A study by Tenuta et al. demonstrated that patients with non-small cell lung cancer (NSCLC) accompanied by sarcopenia have lower levels of CD3-CD56⁺ NK cells and CD56dim natural killer (NK) cells (Tenuta et al., 2023). These findings suggest a potential association between sarcopenia and alterations in immune function among NSCLC patients. CD3-CD56⁺ NK cells and CD56dim NK cells are subgroups of NK cells that play a crucial role in immune response and anti-tumor reactions. Reduced levels of NK cells may lead to a decreased immune response against cancer, thereby increasing the susceptibility and disease progression risk in NSCLC patients. Wang et al. also found a certain correlation between sarcopenia and the neutrophil-lymphocyte ratio (NLR), which is used to assess inflammation and immune status (Wang et al., 2021). An increase in NLR is typically associated with changes in inflammation response and immune function. One possible factor contributing to these changes is the elevation of pro-inflammatory cytokines associated with sarcopenia. Changes in pro-inflammatory cytokines may impact the function of immune cells. These pro-inflammatory cytokines are involved in regulating immune responses and inflammatory processes. For example, elevated levels of IL-6 can trigger inflammatory responses, attract and activate immune cells, and affect various immune cell types, including T cells, B cells, NK cells, and monocytes. Ultimately, this may result in increased proliferation and activation of T cells, promotion of B cell differentiation and antibody production, as well as regulation of NK cell activity (Yadav et al., 2009; Takenaka et al., 2021). Therefore, chronic inflammation may play a significant role in the relationship between sarcopenia and PD-1 inhibitors.

Chronic inflammation is considered an adaptive response to tissue dysfunction or imbalances in homeostasis and is believed to underlie various physiological and pathological processes. Sarcopenia has been associated with chronic inflammation, as it is accompanied by higher levels of inflammatory markers such as IL-6. Elevated levels of IL-6, IL-1β, TNF-α, and C-reactive protein (CRP) have been implicated in the loss of muscle mass and strength in sarcopenia (Icard et al., 2018; Ushitani et al., 2022). Elevated levels of IL-6, IL-1β, TNF-α, and CRP have been identified as potential contributors to the unfavorable outcomes of sarcopenia in PD-1 inhibitor treatment. Previous studies have demonstrated that sarcopenic patients exhibit higher levels of TNF-α, IL-1β, IL-6, and CRP (Lee et al., 2007; Koshikawa et al., 2020; Pan et al., 2021; Shokri-Mashhadi et al., 2021; Chang et al., 2023). IL-6 is primarily produced by monocytes-macrophages, T helper 2 cells (TH2), and other cells, and it plays a role in the differentiation of immune cells. It acts as an endogenous pyrogen involved in inflammatory responses. Due to signaling pathway factors, IL-6 exhibits both pro-inflammatory and anti-inflammatory activities. Pro-inflammatory IL-6 can interfere with skeletal muscle protein synthesis and directly contribute to skeletal muscle protein degradation, resulting in a decrease in skeletal muscle mass. As a classic inflammatory factor, TNF-α also promotes muscle breakdown. Research has found that TNF-α can affect protein expression by inhibiting lipopolysaccharide activity and can exacerbate protein degradation in muscles, promoting muscle breakdown. IL-1β is an intracellular cytokine belonging to the IL-1 family and plays a key role in coordinating innate and adaptive immune responses. Currently, there is relatively limited research on IL-1β and sarcopenia, but studies have shown its potential correlation with grip strength (Rose-John, 2012; Nishikawa et al., 2021a; Shokri-Mashhadi et al., 2021; Chang et al., 2023; Dupont et al., 2023).

Bommarito et al. found that the inflammatory cytokines TNF-α, IL-6, and IL-1β act as negative regulators of PD-1-mediated T cell suppression in vitro (Bommarito et al., 2017). They can reduce the activity or expression levels of PD-1, diminishing the effectiveness of PD-1 binding to its ligands. This implies that T cells may not receive sufficient signals to release inhibition, limiting their ability to eliminate tumor cells. Additionally, the expression level of PD-1 also partially determines the response to PD-1 inhibitors. If the expression level of PD-1 on the surface of tumor cells is low, PD-1 inhibitors may not effectively bind to PD-1 on tumor cells, limiting their therapeutic effect. Furthermore, TNF-α and IL-6 can induce CD4⁺ T cells to secrete soluble PD-1 (sPD-1), which interferes with effective PD-1 binding and further reduces the efficacy of PD-1 inhibitors. Keegan et al. conducted an observational study on NSCLC patients receiving anti-PD-1 treatment and measured 11 plasma cytokines related to immunotherapy response (Keegan et al., 2020). The results showed that decreasing levels of IL-6 were associated with improved PFS. Additionally, this study also observed a correlation between changes in IL-6 and changes in CRP levels. CRP is a protein associated with inflammation and tissue damage and is typically elevated during an inflammatory response. Therefore, the changes in IL-6 and CRP may indicate their association with the inflammatory process. The authors suggested that the decrease in plasma IL-6 and CRP levels was associated with improved prognosis in NSCLC patients receiving anti-PD-1 treatment. In the study of Park et al. involving 125 NSCLC patients receiving PD-1/PD-L1 inhibitor treatment, found that the low IL-6 group (<13.1 pg/mL) had significantly higher ORR and disease control rate (DCR) compared to the high IL-6 group (Kang et al., 2020). Moreover, the low IL-6 group had significantly longer PFS and OS compared to the high IL-6 group. Serum IL-6 levels may serve as a potential biomarker for predicting the efficacy and survival benefits of PD-1/PD-L1 inhibitors in NSCLC. Koeppen et al. conducted observations on the treatment of advanced cancer patients with Atezolizumab (Koeppen et al., 2023). The results showed a correlation between IL-6 and the poor efficacy of Atezolizumab in advanced cancer patients. The IL-6 signal within CD8⁺ T cells may directly inhibit the functionality of cytotoxic T lymphocytes (CTLs), reducing their sensitivity to PD-L1 and resulting in a decreased effectiveness of PD-L1 inhibitors. And Li et al. found in their study that blocking IL-6 promoted the accumulation of CD8⁺ T cells and led to high expression of PD-L1 in colorectal cancer, enhancing the sensitivity of animals to PD-1 therapy (Li et al., 2022a). IL-6 affects the cytotoxic effects and intracellular signaling of CD8⁺ T cells, further influencing the efficacy of PD-L1 inhibitors. By activating the STAT3 pathway, IL-6 inhibits the differentiation of CD8⁺ T cells into cytotoxic effector cells, leading to a tendency for CD8⁺ T cells to remain in an immature or memory-like state rather than developing into cells with cytotoxic effects. On the other hand, the intracellular IL-6 signaling in CD8⁺ T cells limits the response to PD-L1 inhibitors. These mechanisms may collectively reduce the efficacy of PD-L1 inhibitors (Tezera et al., 2020; Li et al., 2022a; Koeppen et al., 2023). In summary, the mechanisms by which IL-6 affects PD-1 inhibitors can be summarized as follows: 1) IL-6 directly suppresses the expression of effector genes in CTLs, reducing their cytotoxicity and effector differentiation capability, thus diminishing the efficacy of PD-1. 2) Indirectly, IL-6 impacts immune cell function by supporting tumor cell survival, inhibiting Th1 responses, promoting the generation of immunosuppressive myeloid cells, and disrupting conventional dendritic cells (cDCs), thereby reducing the efficacy of PD-1 inhibitors. 3) IL-6 promotes the expression of factors involved in memory cell formation, such as Foxo1, IL-10, and Bach2, which may result in CTLs favoring a naïve or memory-like state rather than differentiating into effector cells, ultimately limiting the efficacy of PD-1 inhibitors. It is important to note that the mechanisms of IL-6’s impact can be complex, involving various cell types and signaling pathways. Additionally, the influence of IL-6 on PD-1 inhibitors may vary depending on the specific tumor type and individual differences, necessitating further research in this area (Bommarito et al., 2017; Kang et al., 2020; Keegan et al., 2020; Tezera et al., 2020; Li et al., 2022a; Koeppen et al., 2023) (Figure 3)

PD-1 inhibitors are designed to alleviate the suppressive impact of PD-1 signaling on immune cells, thereby boosting the immune system’s ability to clear mycobacterium tuberculosis infections. Bommarito et al. discovered that TNF-α promotes the generation of sPD-1 in CD4⁺ T cells. sPD-1, though structurally similar to membrane-bound PD-1 (mPD-1), exists in a soluble form in bodily fluids (Bommarito et al., 2017). Elevated sPD-1 production may disrupt the interaction between PD-1 inhibitors and mPD-1 or PD-L1 on cell membranes, potentially compromising PD-1 inhibitor efficacy. Tezera et al. conducted a study using a three-dimensional cell culture model of human tuberculosis infection to investigate the interaction between TNF-α and PD-1 inhibitors (Tezera et al., 2020). The results demonstrated the significant role of TNF-α in tuberculosis, playing a crucial role in an effective host immune response. TNF-α can activate host immune cells and induce cytotoxic activity, production of inflammatory cytokines, to combat mycobacterium tuberculosis infection. When using PD-1 inhibitors for treatment, it may enhance the production of TNF-α and host immune response, leading to excessive TNF-α production. Excessive TNF-α can cause immune-mediated tissue damage and inflammatory reactions, exacerbating the severity of tuberculosis and resulting in a reduced efficacy of PD-1 inhibitors. A mathematical modeling study by Lai et al. on the combined treatment of anti-PD-1 and anti-TNF-α further revealed that TNF-α can promote the production of PD-L1, diminishing the effectiveness of anti-PD-1 drugs (Lai et al., 2020). TNF-α can also activate the expression of T-cell immunoglobulin mucin-3 (TIM-3), allowing cancer cell-expressed Galectin-3 (Gal-3) to block T cells by binding to TIM-3 on the T cell membrane. Additionally, the study showed that the combination of anti-TNF-α therapy significantly reduces resistance to PD-1 inhibitors. In summary, TNF-α may impact the function and interactions of immune cells through various mechanisms, including promoting the production of sPD-1, increasing the expression of PD-L1, activating TIM-3, and inducing immune-mediated tissue damage and inflammatory responses. These mechanisms could potentially diminish the efficacy of PD-1 inhibitors. However, further research is needed to deepen our understanding of the specific roles and underlying mechanisms of TNF-α in PD-1 inhibitor therapy.

Multiple studies on various malignancies have found a positive correlation between IL-1β levels and PD-L1 expression (Bar et al., 2020; Takahashi R. et al., 2021; Lu et al., 2021; Castillo et al., 2023). Aggen et al. conducted a study using a renal carcinoma (RENCA) cell line model of renal cancer and observed that the combination of anti-IL-1β and PD-1 inhibitors effectively enhanced anti-tumor activity. This enhancement was associated with a reduction in immunosuppressive myeloid-derived suppressor cells (MDSCs) and an increase in M1-type tumor-associated macrophages (TAMs) (Aggen et al., 2021). MDSCs can inhibit the activity and function of T cells through various mechanisms, thereby suppressing anti-tumor immune responses. TAMs, on the other hand, are one subtype of macrophages found in tumor tissues. M1-type TAMs are considered to possess anti-tumor activity and can support anti-tumor immune responses and inflammatory reactions through the production of immunostimulatory cytokines and anti-angiogenic factors.

In conclusion, elevated levels of inflammatory markers such as IL-6, IL-1β, TNF-α, and CRP in sarcopenic patients have the potential to influence the efficacy of PD-1 inhibitors. These markers may suppress the activity or expression levels of PD-1 and compromise the binding efficiency between PD-1 and its ligands, thereby limiting the release of inhibitory signals to T cells and diminishing their capacity to eliminate tumor cells. Modulating the levels of inflammatory cytokines could potentially enhance the effectiveness of PD-1 inhibitors. Nevertheless, further research is necessary to fully understand the underlying mechanisms and explore strategies for modulating inflammatory cytokines to improve the therapeutic efficacy of PD-1 inhibitors.

During the body’s fight against infections and maintenance of survival, immune cells undergo continuous changes and adjustments to effectively carry out their defense, surveillance, and homeostasis functions. These changes often require corresponding alterations in the metabolic system to provide the necessary energy and nutrients. Conversely, changes in the metabolic system can also influence the behavior and response of immune cells, thereby tightly linking the immune system with basal metabolic tissues and participating in various life processes. Skeletal muscle, in addition to being a motor organ, plays a crucial role in insulin-induced glucose metabolism. It is involved in the storage, distribution, consumption, and conversion of energy, and is closely connected to overall metabolism and bodily functions. The decrease in muscle mass associated with sarcopenia leads to reduced energy expenditure, which can result in insulin resistance and hinder the effective utilization of glucose and regulation of blood glucose levels (Nishikawa et al., 2021b). Therefore, sarcopenia inevitably impacts overall energy metabolism in the body, and the occurrence of sarcopenia will inevitably have an impact on energy metabolism in the body. Lira et al. conducted a study on metabolic differences between upper and lower limbs after high-intensity intermittent exercise, and the results showed significant differences in metabolic levels between the upper and lower limbs of the participants (Lira et al., 2015). The lower limbs with richer muscles had higher glucose and lactate metabolism rates. Shoemaker et al. studied elderly sarcopenic patients and found differences in skeletal muscle energy metabolism and substrate utilization between sarcopenic and non-sarcopenic participants, with sarcopenic participants showing metabolic inflexibility (Shoemaker et al., 2022). Almeida et al. studied by meta-analysis revealed significantly inadequate intake of energy and nutrition substances with antioxidant potential in sarcopenic patients (Almeida et al., 2023).

Both cancer cells and T cells require energy metabolism to sustain their activities. Cancer cells primarily rely on glycolysis to generate energy, even in the presence of oxygen, a phenomenon known as the Warburg effect. Additionally, cancer cells can utilize protein and fatty acid metabolism to meet their energy and biosynthetic demands for proliferation. T cells, on the other hand, use both glycolysis and oxidative phosphorylation pathways to generate energy during activation. Naive and memory T cells rely more on oxidative phosphorylation, while effector T cells depend more on glycolysis. These distinct metabolic strategies of T cell subsets offer potential targets for metabolic interventions in tumor immunotherapy (Kumar and Chamoto, 2021). PD-1 blockade therapy, by blocking the interaction between PD-1 and its ligand PD-L1, can restore the immune response of T cells against cancer cells. However, if cancer cells can evade immune responses through specific energy metabolism pathways, it may reduce the efficacy of PD-1 blockade therapy. For example, cancer cells can affect immune regulation by releasing metabolites and influencing the expression of immune molecules, limiting the availability of nutrients, and causing microenvironmental acidosis, thereby impairing immune cell function. In addition, if T cells face energy supply insufficiency and metabolic restrictions in the tumor microenvironment, it may reduce the efficacy of PD-1 blockade therapy. Therefore, intervention in these metabolic pathways can help overcome resistance to PD-L1/PD-1 inhibitors, enhance immune cell responses, and improve treatment outcomes (Kumar and Chamoto, 2021; Xia et al., 2021; Laubach et al., 2023).

As previously mentioned, sarcopenia can induce an inflammatory state, which can potentially alter the energy metabolism of immune cells and impact their response to PD-1 inhibitors. Firstly, in an inflammatory state, cells require increased energy to meet the demands of the inflammatory response, leading to a shift towards glycolysis and fatty acid metabolism to meet their energy requirements. This change in energy metabolism may affect the functionality and responsiveness of immune cells. Secondly, the inflammatory state can influence mitochondrial function in cells. Mitochondria are the primary sites for energy production, and the presence of inflammation may lead to mitochondrial dysfunction, resulting in reduced energy production and potentially decreasing the activity and responsiveness of immune cells. Additionally, the inflammatory state can increase oxidative stress and the production of reactive oxygen species, which can damage cells and impact normal functionality (Gaber et al., 2017; Riley and Tait, 2020; Russo et al., 2021). Therefore, the inflammatory state’s influence on the energy metabolism, mitochondrial function, and oxidative stress in immune cells may affect their sensitivity to PD-1 inhibitors and subsequently impact the medication’s efficacy. However, further research is required to better comprehend the mechanisms and implications of the interaction between immune cells and PD-1 inhibitors in the context of an inflammatory state.

In conclusion, sarcopenia can potentially impact the energy metabolism of both T cells and cancer cells. Insufficient energy supply for T cells may reduce their function and responsiveness, leading to a diminished immune response against tumor cells, which may result in decreased efficacy of PD-1 inhibitors. For cancer cells, sarcopenia may lead to energy supply insufficiency and limit the availability of nutrients, enabling cancer cells to evade immune responses and weaken the effectiveness of PD-1 inhibitors. Future research can further investigate the mechanisms of sarcopenia’s impact on the efficacy of PD-1 inhibitors through clinical observations and experimental studies. For example, comparing the differences in energy metabolism pathways, metabolic products, and expression levels of metabolic enzymes between animal models with sarcopenia and without sarcopenia receiving PD-1 treatment; comparing immune cell functions and other indicators. These methods can provide guidance and new intervention strategies for immune therapy in sarcopenic patients.

Exercise has been shown to have positive effects on sarcopenia, particularly in the elderly. It can help maintain skeletal muscle mass, increase muscle strength, and provide anti-inflammatory and antioxidant benefits. In the absence of effective pharmacological treatments for sarcopenia, exercise is considered an ideal approach for prevention and treatment. Resistance training has been found to be an effective strategy for slowing down sarcopenia. It stimulates muscle protein synthesis, improves muscle mass, strength, balance, and endurance (Chen N. et al., 2021). The signaling pathways involving mTOR and FoxO transcription factors play important roles in the development of sarcopenia and muscle atrophy. Resistance exercise can activate the Akt/mTOR signaling system and inhibit the expression of FoxO1/MuRF1 and FoxO3a, thereby promoting positive protein metabolism and inhibiting muscle protein breakdown (Sugimoto, 2012; Yin et al., 2020; Zeng et al., 2020; Hsu et al., 2023).

Aerobic exercise, characterized by rhythmic and repetitive movements, mainly utilizes aerobic metabolism and oxygen to benefit cardiovascular health, body composition, and the heart and respiratory system. It can reduce the expression of catabolic proteins and increase protein synthesis, promoting muscle growth (Park, 2019). Aerobic exercise training also activates mitochondrial biogenesis, improves mitochondrial function and metabolic capacity, reduces oxidative stress and catabolic pathways, decreases muscle protein breakdown, and provides sufficient energy for protein synthesis (Konopka and Harber, 2014). Combining aerobic exercise and resistance exercise can enhance muscle function and cardiopulmonary function, making it an ideal intervention for sarcopenia. Aerobic exercise helps reduce oxidative stress and apoptosis caused by mitochondrial dysfunction, while resistance exercise improves muscle mass and function. High or moderate certainty evidence suggests that the combination of resistance exercise and aerobic exercise is the most effective intervention for improving the quality of life in sarcopenic elderly individuals. Comprehensive exercise programs have been shown to improve body composition and effectively reduce sarcopenia-related risk factors (Yoo et al., 2018; Shen et al., 2023).

Current research suggests that exercise has the potential to improve health outcomes in cancer survivors by increasing muscle mass and reducing sarcopenia. Additionally, for lung cancer patients, exercise can modulate the immune system, effectively reducing levels of inflammatory markers and increasing the production of anti-inflammatory cytokines, which can help alleviate systemic inflammation caused by lung cancer and reduce muscle wasting. Exercise also improves muscle metabolism and function, increasing the rate of muscle protein synthesis and reducing muscle breakdown (Cao et al., 2022; Cortiula et al., 2022). There is evidence to suggest that aerobic exercise training has significant benefits for patients with NSCLC after thoracoscopic surgery (Do et al., 2023). Rutkowska et al. found that NSCLC patients who underwent exercise training demonstrated significant improvements in the 6-min walk test, leading to enhanced physical fitness (Rutkowska et al., 2019). The exercise group also exhibited improvements in lung function parameters, highlighting the benefits of exercise training on lung function. Furthermore, exercise training positively impacted dynamic balance and coordination, reducing the risk of falls. Additionally, respiratory distress was alleviated in the exercise group, suggesting that exercise training may reduce fatigue symptoms and enhance exercise endurance. Hwang et al. demonstrated that exercise training can improve exercise capacity and peak oxygen consumption in NSCLC patients receiving targeted therapy, which is an important predictor of long-term prognosis (Hwang et al., 2012). Preoperative exercise training has also been shown to improve exercise capacity, shorten hospital stay, and reduce postoperative complications in NSCLC patients. Furthermore, Rosero et al. conducted a 10-week exercise intervention program for NSCLC patients showed significant improvements in muscle performance, strength, walking speed, standing ability, and overall physical function in the intervention group (Rosero et al., 2020). However, there is still a lack of research on exercise interventions for muscle in NSCLC patients, and more studies are needed to provide evidence for developing appropriate exercise plans for patients. In conclusion, appropriate exercise plans can be tailored to individual patients’ physical condition, treatment regimen, and abilities, combined with rehabilitation training, to help restore muscle function and strength. Further research is needed to better understand the specific benefits of exercise for NSCLC patients and to develop effective exercise interventions.

Nutritional supplementation has been shown to be effective in delaying and controlling sarcopenia. Combining supplementation with exercise can potentially yield even better results. It is crucial to ensure that patients consume sufficient protein to support muscle repair and growth. Oral nutritional supplements were initially recommended to address inadequate dietary intake and potential malnutrition. Sarcopenic and malnourished patients may struggle to obtain enough protein and other nutrients through diet alone. In such cases, oral nutritional supplements are highly suitable for providing high-quality nutrition (Cawood et al., 2012; Cramer et al., 2016). A prospective study conducted by Cramer et al. on sarcopenic patients for 24 weeks showed that using high-protein oral nutritional supplements can help sarcopenic patients maintain and rebuild muscle mass and strength. In mild sarcopenic patients, compared to the control group’s intake (20 g protein; 499 IU vitamin D3; taken twice daily between meals), the group receiving standard intake (14 g protein, 147 IU vitamin D3; taken twice daily between meals) had more favorable effects on leg muscle strength and mass improvement (Caccialanza et al., 2022). NSCLC patients often experience various degrees of nutritional impairment, leading to chronic inflammation, wasting, and loss of appetite. Anti-cancer treatments themselves, such as radiation therapy, chemotherapy, and surgery, can also cause severe malnutrition in patients. Abnormal nutritional status is correlated with poorer prognosis and the need for more frequent interruptions/delays in cancer treatment (Cramer et al., 2016). A study by Detopoulou et al. on 82 male NSCLC patients showed a potential relationship between a diet rich in potatoes and animal protein and patient prognosis, indicating the crucial role of protein in cancer management and preventing muscle wasting (Detopoulou et al., 2022). However, there is currently insufficient research on the specific protein intake for cancer-related sarcopenic patients. More clinical data is needed to support and establish appropriate nutritional supplementation standards (Ford et al., 2021; Pimentel et al., 2021; Capitão et al., 2022).

One of the characteristics of cachexia in malignant tumors is the significant loss of muscle mass, which is believed to be influenced by chronic systemic inflammation and oxidative stress. Research has shown that serum carnitine levels are lower in cachexia patients compared to healthy controls, with a difference of 8.20 μmol/L (p < 0.000) for free carnitine and 2.60 μmol/L (p = 0.029) for short-chain acylcarnitine. These changes are considered to play an important role in the development of cachexia. Studies have been conducted to supplement carnitine in such patients, and the results have been quite promising (Vinci et al., 2005; Silvério et al., 2011). Levocarnitine is a form of carnitine and a conditionally essential amino acid-like molecule that is primarily found in skeletal muscles. It plays a central role in fatty acid metabolism and exhibits significant antioxidant and anti-inflammatory properties. Animal studies have shown that supplementation with a 28-day dose (0.1 g) of levocarnitine can promote muscle recovery (Silvério et al., 2011; Evans et al., 2017). Evans et al. conducted a study on middle-aged and elderly individuals and found that supplementation with a combination formula containing 1,500 mg/day of levocarnitine (along with leucine and creatine) for 8 weeks increased muscle mass by 1.0 kg, significantly improved lower limb lean mass, calf strength, and non-trunk lean mass (Evans et al., 2017). The combination of levocarnitine and leucine in the formula can stimulate muscle protein synthesis when combined with whey protein isolate, while creatine can increase muscle mass and strength. The addition of levocarnitine can increase the bioavailability of branched-chain amino acids and reduce protein degradation, possibly due to improved protein metabolism through the mTOR pathway. Kraft et al. conducted a study on pancreatic cancer patients and found that supplementing with levocarnitine for 3 months significantly increased body weight, improved body composition, and improved quality of life in advanced pancreatic cancer patients. Levocarnitine may have potential therapeutic effects on cancer cachexia (Kraft et al., 2012).

Future research can investigate more precise nutritional intake strategies, encompassing diverse protein types and sources, along with the synergistic utilization of nutritional supplementation and exercise training. Personalized nutritional interventions based on individual characteristics and metabolic status hold promise as a research direction. Through further clinical research and long-term follow-up observations, a better understanding of the effects of different intervention strategies on sarcopenia can be gained, leading to the development of more specific nutritional treatment plans for NSCLC patients receiving PD-1 inhibitors.

Drug intervention is another avenue worth considering. Anamorelin is a medication that has been investigated for its potential in ameliorating cancer cachexia. Presently, Anamorelin has received approval in certain countries for treating cancer cachexia in select cancer patient populations. Anamorelin may improve cachexia through multiple mechanisms. As a Ghrelin receptor agonist, it can increase appetite and promote protein synthesis and muscle mass. Additionally, Anamorelin may also alleviate muscle wasting caused by cachexia by inhibiting the signaling of cytokines such as Myostatin, Activin-A, and TGF-β, which are considered important negative regulators of skeletal muscle mass. Therefore, Anamorelin may increase muscle mass and reduce muscle wasting by inhibiting the activity of these cytokines (Wakabayashi et al., 2021; Hanada et al., 2022; Takayama et al., 2023). However, clinical observations conducted by Dawson-Hughes et al. showed that Anamorelin did not significantly change muscle mass but may improve lower limb strength (Dawson-Hughes et al., 2024). While Anamorelin exhibits promise in ameliorating cancer cachexia, further research and exploration are necessary to comprehensively understand its precise mechanisms of action and its effects on sarcopenia. Additionally, the efficacy and safety of Anamorelin require further evaluation to ascertain its optimal utilization in clinical practice.

Throughout the course of cancer treatment, side effects like nausea, vomiting, fatigue, and loss of appetite can adversely affect patients’ nutritional intake. Therefore, healthcare professionals provide appropriate nutritional management, preventive education, and other measures as necessary to prevent iatrogenic sarcopenia (Nagano et al., 2019). Some treatment drugs can also cause muscle loss, such as glucocorticoids, and PD-1 inhibitors can stimulate the gastrointestinal tract, thereby interfering with nutrient intake (Klein, 2015; Cheng et al., 2023). Therefore, addressing iatrogenic and drug-induced sarcopenia is essential for patients. In combination with the aforementioned nutritional therapy, healthcare professionals can develop personalized nutrition plans, provide appropriate nutritional support based on the specific circumstances of the patient, and suggest the adoption of frequent small meals to avoid prolonged fasting, increase the frequency of eating, relieve the burden on the digestive system, alleviate treatment side effects, maintain metabolic stability and adequate nutrition (Barry, 2018). To address gastrointestinal reactions during PD-1 inhibitor treatment, healthcare professionals should closely monitor patients’ condition, evaluate the impact on their nutritional intake, implement suitable dietary adjustments and medication support as needed, and collaborate with gastroenterology specialists to prevent additional muscle loss.

Cancer patients often face emotional and psychological stress, accompanied by chronic inflammation and immune system dysfunction. These factors can eventually lead to the occurrence of depression, and depression has a more severe impact on lung cancer patients compared to other types of cancer. Depression has been identified as a prognostic factor for the survival rate of NSCLC (Andersen et al., 2023). Li et al. analyzed NSCLC patients with depression and found that the group with depression had a lower PFS compared to the group without depression (Li et al., 2022b). There were statistically significant differences in ORR and DCR between the two groups, indicating that depression can affect the efficacy of chemotherapy combined with immunotherapy. Sarcopenic patients, like cancer patients, face elevated inflammatory factors, immune dysfunction, and limited physical activity, and therefore, also face depression issues. Szlejf et al. conducted a study on sarcopenia and depression among 5,927 participants aged 55 and above, and the results showed a correlation between depression and sarcopenia as well as low muscle strength (Szlejf et al., 2019). Chang et al. analyzed the relationship between sarcopenia and depression in 10 studies on myopenia, and the results also showed an independent correlation between sarcopenia and depression (Chang et al., 2017). In conclusion, NSCLC patients who develop sarcopenia may also experience depression. Depression not only affects the prognosis of NSCLC patients but also influences the effectiveness of PD-1 inhibitors. Cohen et al. observed 62 patients with advanced cancer receiving ICIs treatment and found that psychological issues can affect treatment outcomes through pro-inflammatory cytokines and Soluble cytotoxic T-lymphocyte-associated antigen 4 (sCTLA-4) (Cohen et al., 2023).

In summary, providing psychological support and rehabilitation psychology services to help patients cope with emotional and psychological distress and improve their motivation and self-management abilities is crucial. Firstly, it is important to provide patients with emotional support, helping them understand and cope with the emotional reactions they may experience, such as anxiety, fear, and depression. By offering emotional support, patients can better face the challenges of cancer and seek positive coping strategies. Secondly, assisting patients in adjusting their cognition and attitude towards cancer and helping them develop a positive mindset is essential. Providing effective coping strategies is also necessary to help patients navigate the various challenges during cancer treatment. This may include techniques and tools for managing treatment side effects, pain management, and adapting to lifestyle changes. Lastly, using the principles of rehabilitation psychology, helping patients improve their self-management abilities, including skills for diet, exercise, sleep, and stress management, contributes to enhancing their quality of life and overall rehabilitation outcomes.

Regular evaluation of muscle mass and function is crucial for patients, and monitoring their muscle health is an essential measure. In addition to routine instrumental methods such as CT, MRI, DXA, and BIA for skeletal muscle examination, grip strength, gait speed, SARC-F, SARC-F combined with calf circumference (SARC-CalF), and grip strength testing can also be used for convenient self-testing by patients and their families. Grip strength threshold: Men: <26 kg, Women: <18 kg; Gait speed threshold: ≤0.8 m/s; SARC-F includes: 1) Lifting/carrying a 10-pound weight; 2) Walking across a room; 3) Getting up from a bed or chair; 4) Climbing 10 flights of stairs; 5) Number of falls in the past year, with three scoring options (easy: 0 points; moderately difficult: 1 point; difficult/unable to complete: 2 points). SARC-F ≥ 4 is indicative of sarcopenia; SARC-CalF is based on SARC-F and incorporates calf circumference (men <34 cm, women <33 cm). A score of 10 is assigned if calf circumference is below the threshold; a score of 0 is assigned if it is above the threshold (Forsythe et al., 2020). Healthcare professionals can adjust treatment measures based on the assessment results and promptly implement intervention measures.

It is worth noting that there may be differences in the occurrence of dermatomyositis between males and females due to the influence of sex hormones and the disparity in body composition, with different diagnostic cutoff points (Janssen et al., 2002; Sipilä et al., 2013; Grossmann, 2014; Sugioka et al., 2016). Gender influences the expression of PD-1 in tumors and the efficacy of ICIs. Firstly, studies have found that the incidence of lung cancer in females is continuously increasing, and female patients are more prone to develop adenocarcinoma compared to males. Inherent and adaptive differences in immune responses between males and females contribute to the gender-related disparity in the response to PD-1/PD-L1-dependent immunotherapy (Gu et al., 2022). Gu et al. have found that female lung cancer patients exhibit higher levels of sPD-1 in serum and PD-1 expression on CD4⁺ T cells compared to male patients (Gu et al., 2022). Another study has shown that male patients experience greater improvements in OS and PFS when receiving immune checkpoint inhibitor therapy compared to female patients (Wu et al., 2018). A meta-analysis has also demonstrated that anti-PD-1/anti-PD-L1 monotherapy is highly effective in male patients but not in female patients, even in NSCLC with high PD-L1 expression levels (Conforti et al., 2021). These research findings indicate the significant impact of gender on PD-1 expression in tumors and the efficacy of ICIs. Further investigation into the mechanisms underlying gender differences is of great significance for optimizing tumor treatment strategies and enhancing personalized therapeutic outcomes. Although there are currently no specific intervention measures and recommendations to consider the effect of gender on the efficacy of PD-1 inhibitors in dermatomyositis, understanding the influence of gender differences on dermatomyositis is important for personalized treatment and optimizing therapeutic efficacy. Future research may explore the impact of factors such as sex hormones on the pathogenesis of dermatomyositis and further investigate the role of gender in PD-1 inhibitor therapy. This will contribute to providing more effective treatment options and intervention measures for patients.

The above strategies need to be individualized based on the patient’s specific condition and treatment plan, in collaboration with the medical team and nutritionists, ensuring the safety and suitability of the strategies. Additionally, establishing positive communication and education with patients, encouraging their active participation in measures to prevent sarcopenia, and ensuring their understanding and compliance with the strategies are important. In conclusion, by early intervention and active management of sarcopenia, the impact on the efficacy of PD-1 inhibitors can be mitigated, improving treatment outcomes and survival rates for patients.