cDC1s, particularly in humans, are characterized by the presence of CD141 on their cell surface. Migratory subsets exist in lymph nodes and peripheral tissues (29). The cellular indication markers that make out cDC1 are Clec9A⁺, Sirp (CD172)⁻, CD11c⁺, CD11b⁻, CD141⁺, CD123⁻ and HLADR⁺ (26). cDC1 is chiefly responsible for antigen cross-presentation and plays an essential part in anti-viral and tumor immune responses. CD141⁺DC expresses Toll-like receptor 3 (TLR3) at high levels, produces INF-β and IL-12p70, induces superior Th1 response, and can sense pathogen-associated molecular patterns (PAMP) through TLR3. Moreover, poly I:C-actived CD141⁺DC has a high ability to cross-submit soluble protein antigen (Ag) to CD8⁺ cytotoxic T lymphocytes by MHC I, leading to inducing an adaptive immune response (30). IL-12 secreted by cDC1 can active NK cells to produce IFN-γ (31). The cDC1 of mouse lymphoid organs chiefly expresses CD8α, Clec9a, Xcr1 on the surface. And in the non-lymphoid tissues, cDC1 expresses CD103 (32).

In recent years, drug targeting cDC1s as an anti-tumor therapy has achieved promising clinical efficacy. In animal and clinical trials, it has been found that B-cell lymphoma 2 (BCL2) can act as a specific immune checkpoint for cDC1s, activating cDC1s and thus promoting anti-tumor immunity (33, 34).

The cell surface factors that make out cDC2 are Clec9A⁻, CD123⁻, HLADR⁺, CD11c^hi Sirp⁺ and CD1c⁺ (35–37). Myeloid cDC2 is similar to monocytes, and expressed extensive lectins, RIG-I-like receptors, Nod-like receptors and Toll-like receptors (27). They play a vital role in autoimmune diseases and anti-bacterial defense and in keeping the immune tolerance (38). cDC2 has been shown to induce Th1, Th2 and Th17 cells (39, 40). Two new subtypes of CD1c⁺ have been identified. Human CD1c⁺CLEC10A⁺CLEC4A^lo cDC2s and CD1c^loCLEC10A^–CLEC4A^hi cDC2s, are the equal to mouse T-bet^-cDC2s (‘cDC2B’) and T-bet⁺cDC2s (designated ‘cDC2A’), severally. T-bet^– cDC2s more likely to cause inflammation, while T-bet⁺cDC2s show transcripts encoding molecules participated in repairing of tissue and own a reduced capacity to polarize naive T cells (41). In mouse, cDC2 have a more heterogeneous expression of Sirpa, CD11b, and other on the surface (42, 43). James et al. found that in pancreatic adenocarcinomas (PDACs) patients, cDC2s were systematically suppressed by significantly increased IL-6, as IL-6 disrupted the polarization of cDC1s and cDC2s, impaired antigen processing and presentation functions, resulting in anti-tumor immunity being affected (44). Luo et al. found that blocking Tim-3 in cDC2 promoted CD4⁺T cell and enhanced the anti-tumor ability of ADU-S100(S100), an agonist for Stimulator of interferon genes (STING) (45).

pDC, which are found in blood and lymphoid tissues, and certain organs like the lung in mice and tonsils in humans (29). pDCs can be characterized by cell surface markers CD11c^lo, CD123⁺, HLADR⁺, BDCA2 (CD303)⁺, BDCA4 (CD304)⁺, CD45RA⁺ (46, 47). After recognizing the virus or its own nucleic acid by Toll-like receptor 9 (TLR9) and TLR7 (47), pDC produces a significant amount of type I interferon (IFN) as well as a small amount of III IFN (48), acting as an antiviral agent (49, 50). Type I IFN is crucial for the cross-presentation of CD8α⁺ DC and the development of tumor antigen specific CD8⁺ T cell in vivo (51). pDC also produces various chemokines and cytokines like CC chemokine receptor 4 (CCL4), CCL3, CXC chemokine ligand 10 (CXCL10), CXCL8, IL-6 and IL-12. pDCs submit antigens to CD4⁺T cells through co-stimulatory molecules and MHC II (47). Cha et al. found the enrichment of pDCs was closely related to the prognosis of smoking-induced lung cancer (52).

MoDCs, which reside in the skin, lung, and intestine, can be identified by specific cell surface markers including CD11c⁺, HLADR⁺, CD14⁺, CD11b⁺, CD1c⁺, CD209⁺, CD206⁺, CD64⁺, CCR2⁺, CD1a⁺ and CD172a⁺ (29). MoDC is primarily produced in response to inflammation and promotes environmentally dependent division of CD4⁺ T cells into the type 2 helper T cells (Th2 cells), type 1 helper T cells (Th1 cells), or IL-17-producing helper T cells (53). Additionally, MoDCs secrete numerous inflammatory cytokines and participate in the partial inflammatory response (54). Raccosta et al. found a new antagonist of the oxysterol receptors called Liver X Receptors (LXRs) promoted the differentiation of MoDCs within tumors and enhanced their anti-tumor effects in mice (55).

Here we summarize the subsets of dendritic cells in Table 1 .

The studies by G. Cai and colleagues demonstrated that Alhagi honey polysaccharide (AH) conferred various benefits on mice by promoting the maturation of dendritic cells (DCs) and enhancing the production of CCL20, which aggregates DCs. This aggregation induced the activation of B cells, CD8⁺ and CD4⁺ T cells. Additionally, AH augmented the secretion of secretory IgA (sIgA) to protect the intestine. This is accomplished either by stimulating Th cells to divide and produce cytokines or by directly activating DCs to release cytokines, thereby increasing the number of IgA⁺ cells, J chain, and pIgR in the gut. AH also significantly elevated the levels of short-chain fatty acids (SCFAs) in the caecum, thereby helping to regulate cyclophosphamide-induced intestinal immune dysfunction. In vitro experiments further revealed that AH markedly enhanced pIgR protein expression in Caco-2 cells and promoted the maturation of DCs to regulate immune responses (58). Comparing the immune effects of Echinacea purpurea polysaccharide (EPP) and sulfated EPP (sEPP) on chicken bone marrow-derived DCs (chBM-DCs), L. Yao et al. found that both EPP and sEPP enhanced the expressions of CD11c and CD80, improved the capability of chBM-DCs to promote the proliferation of allogeneic mixed lymphocytes, and significantly increased the levels of IL-2 and IFN-γ, while down-regulating the levels of IL-4 and IL-10 (59). Y. Wu et al. found that Glycyrrhiza polysaccharide extract 1 (GPS-1) enhanced the generation of IFN-γ and IL-4, and increased the ratio of CD3⁺CD4⁺ T and CD3⁺CD8⁺ T lymphocytes in the mice spleen. Further experiments revealed that GPS-1 promoted maturation and phagocytosis of DCs. Similarly, H. Zhou et al. (60) also demonstrated that GPS-1 was able to enhance the secretion of IL-12, TNF-α and IFN-γ as well as promoted the secretion of NO, IL-2, IL-1β, IFN-β, TNF-α and IL-12p70 from DCs (61). In studies conducted by Y. Wu et al., the experiments in vitro showed that the acidic Epimedium polysaccharide (EPS-1) increased the proliferation of the splenic lymphocytes and the production of cytokines (IFN-γ, IL-2, TNF-α and IL-4). Furthermore, the expression of surface molecules of mature chBM-DCs (MHC II, CD11c, CD40 and CD86) and the levels of cytokines (IL-10 and TNF-α) were increased, and EPS-1 also enhanced phagocytosis rate of mature chBM-DCs (62, 63). Y. Zou et al. have observed that purified Achyranthes bidentata polysaccharide (ABP) promoted the upregulation of MHC II, CD40 and CD86 expressions, inducing the maturation of DC phenotypes. Moreover, ABP was demonstrated to enhance the production of IL-12 (64). X. Wang et al. found that Isatis root polysaccharide (IRPS) promoted the maturation of MoDCs, induced the secretion of IL-12, and reduced the expression of IL-6 (65). Y. Huang et al. found that Rehmannia glutinosa polysaccharide (RGP) significantly stimulated lymphocyte proliferation, and enhanced the production of IFN-γ and IL-2. The antigen presenting ability of DCs was also improved by RGP stimulation (66). J. Gao et al. found that Plantain polysaccharide (PLP) exhibited the ability to promote the maturation of DCs both in vivo and in vitro. In mouse model of breast tumors 4T1, PLP effectively controlled tumor growth and enhanced immune response by recruiting DC, CD8⁺T and CD4⁺T cells to the tumor microenvironment (67). M. Tian et al. found that Huangqi Guizhi Wuwu Tang (HGWT) displayed potent anti-tumor effect. Polysaccharides derived from Astragalus membranaceus and Polyporus umbellatus were demonstrated to promote DCs maturation (68).

X. Zhao et al. discovered that Salidroside liposome effectively promoted the maturation of DCs. Additionally, it was found to stimulate MLR proliferation and enhance antigen presentation. Furthermore, Salidroside liposome was able to induce sustained cellular and humoral immune responses (69). C. Mo et al. found that Ginsenoside-Rg1 (G-Rg1) exerted its anti-fibrotic properties by reducing DC maturation mediated by IDO1 (70). H. Guo et al. found that Astragaloside IV (ASI) effectively promoted the maturation of DC phenotype, by means of significant upregulation of CD14, CD40, CD80, CD83, CD86 and HLA-DR. Additionally, ASI treatment enhanced the release of IL-12, thereby bolstering the immune response (71).

S. Nabeshima et al. found Hochu-ekki-to (HOT) stimulated DCs to mature in a dose-dependent manner by increasing the expression of CD83, CD86, CD80 and by producing IL- 12 (72). Y. Fu et al. found that Myrothecine A was able to promote the expression of CD86 and CD40 on DCs (73). D. F. Huang et al. discovered that the Plantago asiatica L. seeds extract (ES-PL) induced DC maturation with high level of MHC II and key stimulatory molecules CD80 and CD86. Functional maturation of ES-PL-treated DC was demonstrated by reduced mannose receptor-mediated endocytosis and strengthened antigen presentation to allogeneic naive or homogeneously activated T lymphocytes. Additionally, the gene expression of CCR7 in ES-PL-treated DC was also enhanced (74). C. Y. Li et al. observed that Cordyceps sinensis had the ability to promote DC maturation. Cordyceps sinensis was found to stimulate the expression of costimulatory molecules on DCs, to increase the expression of the inflammatory factors, and to enhance the proliferation of allogeneic T cells. These findings suggested that Cordyceps sinensis has the potential to strengthen DC function and stimulate anti-tumor immune responses (75). N. Takeno et al. discovered that Shi-Quan-Da-Bu-Tang (SQDBT) enhanced OVA antigen phagocytosis and antigen presentation in DCs in vitro. In addition, in mice inoculated with mouse lymphomas expression tumor antigens, the researchers observed a significant decrease in tumor growth and a prolongation of survival when SQDBT was administered (76). M. Kaneko et al. found that Hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang) (HOT) significantly reduced OVA-specific IgG1 and IgE serum levels and antigen-specific proliferation of the cells in splenic organ of young mouse. HOT increased the amount of CD4⁺T cells and enhanced expressions of MHC II and CD86, CD80 and CD40 on antigen-presenting cells (77).

The researchers mentioned above have largely explored the anti-tumor properties of CHM, emphasizing the augmentation of MHC I and II expression, CD40, CD80, and the secretion of specific inflammatory factors. However, several important considerations arise. Firstly, there has not been a more detailed examination of the signaling pathways implicated in these processes. Secondly, the majority of these studies are conducted in vitro and focus on the modulation of DC function by CHM. Only a limited number of studies have been extended to animal models, and there is a significant absence of clinical trials to confirm these observations. These issues certainly merit our thorough attention and further investigation.

TLRs play a crucial part in the activating innate immunity by recognizing specific microbial signatures, and are essential components of both the innate and adaptive immune systems. A series of studies have shown that TLRs signaling pathways were composed of two main components. The first is the MyD88-dependent pathway shared by all TLRs. The second is the MyD88-independent pathway specific to the TLR3- and TLR4 pathways (78). TLRs are widely expressed in various immune cells, and apart from tumor-infiltrating immune cells, other tumor also exhibit TLR activation (79, 80). Within the TLR family, TLR4 is particularly important for the maturation of DCs. MyD88 (myeloid differentiation primary response gene 88), which contains TIR (Toll-interleukin-1 receptor) domain, is an adaptor protein involved in the TLR4 pathway. TRAF6 (TNF receptor-associated factor 6), another adaptor protein, is crucial for the recruiting of IRAK1 in MyD88-dependent pathway (81). MyD88 activates TRAF6 and the downstream transcription factor NF-κB, thus promoting the generation of inflammatory factors.

Pearce et al. found that the activation of TLRs led to an early rapid increase in the rate of glycolysis within DCs. This metabolic shift supported the expansion of the Golgi and endoplasmic reticulum apparatus in DCs, which was necessary to accommodate the enhanced transport, protein synthesis, and cytokine secretion that were crucial for DC activation (82). J. J. Kim et al. found that the B-chain of Korean mistletoe lectin (KML-B) increased the expression of co-stimulatory molecules (MHC II, CD86, CD80 and CD40) and the secretion of cytokines (TNF-α, IL-12p70, IL-6 and IL-1β). Furthermore, KML-B influenced other markers of BMDCs maturation such as antigen uptake and CCR7 expression. The capacity of KML-B to improve BMDC features was depend on the expression of TLR4. Besides, naive CD4⁺T cells were directly or indirectly induced to differentiate into Th1 cells by KML-B matured BMDCs (83). S. Tanaka et al. proved that Chrysanthemum coronarium L. (C. coronarium) edible plant extracts significantly activated immune response through TLR9-, TLR4- and TLR2-dependent way. Stimulation with C. coronarium extract immediately activated CD11c⁺ DCs, leading to DC maturation characterized by increasing the expression levels of MHC II, MHC I, CD86, and CD40, and the production of IL-12 (84). X. Duan et al. found that Lycium barbarum Polysaccharides (LBP) promoted mature DCs in mice through TLR4-Erk1/2-Blimp1 signaling pathway. They discovered that LBP treatment induced DC maturation by upregulating MHC II and co-stimulatory molecules (CD80, CD86) and increasing the generation of IL-6 and IL-4 (85). X. Li et al. found that Radix Glycyrrhizae polysaccharide (GP) strengthened the generation of MHC I-A/I-E, CD86 and CD80 on DCs. It also facilitated the proliferation of allogenic CD3⁺T cells and the secretion of IFN-γ, while inhibiting the endocytosis of DCs on FITC-dextran. Additionally, GP increased the production of IL-12p70 in DCs in a time-dependent manner. Of note, the increase in IL-12p70 production was strongly suppressed by NF-κB, TLR4, p38 MAPK or JNK inhibitors, suggesting that GP was partially recognized by TLR4, and activation of MAPKs and NF-κB pathways may led to enhancing DC maturation (86). J. Du et al. investigated the effect of Actinidia eriantha Benth polysaccharide (AEPS) on DCs. They observed that AEPS decreased the BMDC phagocytosis and enhanced the expression of co-stimulatory molecules. AEPS also increased cytokines (IL-12p40, IL-10, IL-6, TNF-α, IL-1β, IFN-β and IFN-γ) and chemokines (CCL5, MIP-1α, MIP-1β, MDC and MCP-1). AEPS primarily exerted its effects through the TLR2/4 and NF-κB pathway to enhance DC maturation and functionality, thereby augmenting anti-tumor immune responses. The study also revealed elevated expression levels of STAT1, STAT2, and STAT5b, indicating the influence of JAK-STAT signaling on DC function (87). R. Bo et al. found that through TLR4 signaling pathway, Lycium barbarum polysaccharides liposomes (LBPL) significantly enhanced the proliferation of mouse DC precursor cells, and upregulated the expression of co-stimulatory molecules (CD86, MHCII and CD80) and cytokines (TNF-α, IL-12p40) to promote DCs maturation. The study further confirmed that LBPL upregulated the expression of TRAF6, MyD88, TLR4, NF-κB genes, and proteins (88). J. K. Wang et al. found that Matrine strengthened the secretion of inflammatory cytokines mediated by the TLRs signaling pathway to exert an anti-tumor effect. Matrine drastically enhanced the mRNA expression of TLR8, TLR7, MyD88, IκB kinase (IKK) and TRAF-6, as well as the protein expression of TLR8 and TLR7. In addition, Matrine also strengthened the expression of MHC-II, CD40, CD86, CD80 and CD54 in DCs, and stimulated the secretion of IL-6, IL-12 and TNF-α (89). Y. Tian et al. found that Astragalus mongholicus (AMs) promoted the expression of CD11c and DCs maturation in a dose-dependent manner. This effect was mediated by up-regulating TLR4 and inhibiting IκB-α (90). D. Wang et al. have summarized the impacts of Astragalus polysaccharide (APS) on immune cells. They found that APS significantly increased the proliferation of CD8⁺ T and CD4⁺ T cells and enhanced the expression of CD40, CD80, and CD86 in DCs. APS also enhanced the production of IL-12 and TNF-α, and induced the Th1/Th2 shift towards Th1 (32) (91). Zhou et al. found that APS activated DCs through the MyD88-dependent signaling pathway mediated by TLR4. When the TLR4 was activated by ligand, the TIR domain of the MyD88 protein was bound to the TIR domain of TLR, activating downstream TRAF-6. This, in turn, activated NF-κB, facilitating its entry into the nucleus and the subsequent activation of transcription of genes related to DC maturation. The activated DCs then expressed co-stimulatory molecules and related cytokines (92). J. Li et al. found that after treatment with Pleurotus ferulae water extract (PFWE), BM-DCs dose-dependently regulated the expression of CD86, CD80, CD40, and MHC II, and also strengthened the production of TNF-α, IL-6, and IL-12, primarily mediated by the TLR4 signaling pathway. Moreover, PFWE induced DCs to enhance the proliferation of allogeneic CD8⁺ T cells and improved their capacity to present antigens to autologous CD8⁺ T cells (93). T.-Y. Jung et al. found that Uncaria rhynchophylla ursolic acid extract enhanced the generation of CD83, CD80, CD1a, CCR7, HLA-DR and CD86 on DCs, promoted the proliferation of T cells, and strengthened the secretion of IFN-γ and IL-4. The production of IL-12p70 was induced by TLR2 and TLR4 signaling pathways, thereby inducing T cell differentiation to Th1 subtype (94). In addition, K. S. Kim et al. also found that Uncaria rhynchophylla (Miq.) Miq. ex Havil. uncarinic acid C extract (URC) enhanced the expression of CD40, CD38, CD1a, CD83, CD80, CD54, CCR7, HLA-DR and CD86 on DCs, and also promoted the production of IL-12p70 through TLR2 and TLR4 signaling pathways, leading to the conversion to Th1 subtype and the production of substantial amounts of IFN-γ. URC also prompted DCs to induce NF-κB transcription factor. DCs treatment with URC demonstrated moderate migration capability to CCL19 and CCL21 (95).

The NF-κB pathway plays a pivotal role in the anti-tumor process, being a key downstream molecule of TLR4 (96). This pathway is composed of two branches: canonical and non-canonical pathways. And it is well known for its activity in responding to a series of external stimuli, such as immune response, cell proliferation, survival, and differentiation (97–100). Dysregulated NF-κB activity has implicated in inflammatory diseases and tumors, making it as a potential therapeutic target (101). IκB-α is the main regulatory protein that inhibits nuclear translocation. Numerous studies highlighted the interplay between NF-κB and MAPK signaling pathways in DCs activation and maturation (102). Studies have revealed that interferon (IFN) and NF-κB pathways were highly enriched in mature cDC1s associated with tumors. And the IFN response genes, which is necessary for anti-tumor immunity contained in cDC1, are regulated by IFN regulatory factor 1 (IRF1)-dependent NF-κB. Activated NF-κB promotes the recruitment and activation of CD8⁺T cells, which are important in orchestrating anti-tumor immunity (103).

E.-Q. L et al. found that Lycium barbarum Polysaccharides (LBP) induced the maturation of DCs, increased the production of IL-12p70 and IFN-γ, and promoted the expression of NF-κB in MLR, suggesting that these effects were associated with the NF-κB pathway (104). B. Zhao et al. discovered that a CHM formula Yangyinwenyang (YYWY) significantly inhibited tumor development in a mouse model of Lewis NSCLC. YYWY was found to promote DCs maturation through MAPK and MyD88-NF-κB pathways. This led to the generation of cytokines such as IL-2, IL-1β, IFN-γ, IL-12, and TNF-α from DCs. In addition, DCs matured under YYWY enhanced T cell proliferation and promoted differentiation of Th1 and CTL, thereby increasing the Th1/Th2 ratio (105).

MAPK pathway activation was a common feature in many types of cancers (106, 107). JNK, ERK and p38 MAPK pathways are often deregulated in cancers, and these pathways regulate the expression and activity of key inflammatory mediators, including proteases and cytokines, which may function as effective cancer promoters (108). Wang et al. found that inhibition of p38 MAPK restored the function, phenotype and cytokine secretion of BMDCs affected by tumor culture conditioning medium, thereby activating allospecific T cells, increased the expression of DC surface molecules, and enhanced the production of IL-12 (109).

T. Qin et al. modified polysaccharides extracted from Hericium ericium (HEP) to produce its nine selenium derivatives, sHEP1-sHEP9. Among them, sHEP1, sHEP2 and sHEP8 were found to increase the expression of MHC-II and CD86 on DCs, triggering their maturation. Additionally, sHEP2 and sHEP8 significantly reduced DCs endocytosis and strengthened the productions of cytokines (IL-12 and IFN-γ). Mechanistically, sHEP2 was found to promote the phosphorylation of JNK, p38 and ERK, as well as the nuclear translocation of p-c-Jun, p-CREB and c-Fos. Furthermore, sHEP2 also activated NF-κB pathway, leading to the decrease of the IκBα/β and nuclear translocation of p65 and p50 (110). Moreover, R. Yu et al. discovered that HEP also promoted DC maturation, with increased MHC II and CD86 expression, typical morphology, low antigen uptake, elevated TNF-α and IL-12 levels, and upregulation of MyD88, TLR4 and NF-κB proteins (111). D. H. Kim et al. found that 6-Acetonyl-5,6-dihydrosanguinarine (ADS) obtained from Chelidonium majus L. activated ERK/JNK phosphorylation in DCs by inducing ROS. This phosphorylation activated the NK-κB pathway, subsequently triggering the production of inflammatory cytokines, including TNF-α, IL-6, and IL-8 (112). J. Pan et al. found that Huaier extract enhanced the infiltration of CD4⁺ T cells and promoted DCs maturation in mice with 4T1 breast cancer. Huaier promoted the expression of co-stimulatory molecules in DC2.4 and BMDCs, as well as enhanced the levels of IL-12p70 and IL-1β, while inhibited their phagocytosis activities. Furthermore, Huaier promoted the proliferation of CD4⁺T cells, induced their differentiation into Th1 cells, which was achieved by modulating of the PI3K/Akt and MAPK pathways. Huaier increased the expression of p-Akt, Akt, PI3K, p-JNK, and JNK in BMDCs, while reduced the expression of p-p38 MAPK (113). N. Perera et al. found that the galactomannan isolated from Antrodia cinnamomea (ACP) stimulated the production of IL-6 and TNF-α in human monocyte-derived DCs through engagement with TLR4. ACP achieved this by activating MAPK and protein kinase C-α (PKC-α) phosphorylation, leading to the increased the phosphorylation of p38, JNK1/2 and ERK1/2. Furthermore, ACP induced TNF-α secretion and COX-2 expression via PKC-α (114).

In addition, research has shown that CHM regulates DCs function through various signaling pathways, including the STATs pathway. The JAK/STAT pathway is particularly important in malignant tumors, with its inhibition holding therapeutic potential. One key regulator involved in the negative regulation of the JAK/STAT pathway is SOCS1, which exerts its effects through modulating phosphorylation states (115). JAK signals activate STAT-related transcriptional activity, driving gene expressions that control maturation, differentiation, and function in DCs (116).

In Chinese Herbal Medicine, there is a formula (SL) which consists of Lonicerae Japonicae Flos and Sophorae Flos. Y. X. Liu et al. found that treatments with an ethanolic extract of SL (SLE) increased the infiltrations of cytotoxic T cells (Tc), helper T cells (Th), and DCs in both melanoma tumors and spleens of mice. Furthermore, SLE was found to inhibit STAT3 activation in B16F10 cells, and to down-regulate the mRNA levels of STAT3 target genes in splenic lymphocytes (117). Y. Wang et al. discovered that the extract from Pinellia pedatisecta Schott plant, known as PE, had several beneficial effects on the immune response against tumors. They found that PE promoted the expression of MHC II and co-stimulatory molecules CD86 and CD80 on tumor-associated dendritic cell (TADCs), induced the production of IL-12 by TADCs, and enhanced the proliferation of both CD8⁺ T and CD4⁺ T cells. Moreover, PE induced the differentiation of GZMB⁺ CD8⁺ T and IFN-γ⁺ CD4⁺ T cells. In vivo experiments, PE strengthened the proliferation of cytotoxic T cells, as evidenced by increased expression of GZMB, CD137, Ki67, or TNF-α, IFN-γ. PE reversed the expression of PD-1 or CD95. The researchers confirmed that PE down-regulated SOCS1 expression and the phosphorylation of JAK2, STAT1, STAT4 and STAT5 in a time- and dose-dependent manner (118, 119).

J. Tian et al. found that Ficus carica Polysaccharides (FCPS) was able to effectively promote maturation of DCs through dectin-1/Syk pathway, leading to increased CD40, CD80, CD86 and MHC II expression. FCPS also stimulated DCs to produce cytokines, such as IL-6, IFN-γ, IL-12, and IL-23. Furthermore, FCPS enhanced the capacity of DCs to stimulate T cells and promoted T cell proliferation (120). F. Yao et al. discovered that Yupingfeng Granule (YPF) enhanced the proportion of mature DCs in tumors and adjacent tissues in mouse models of hepatocellular carcinoma. YPF treatment also led to a reduction in Th2 levels, an increase in Th1 levels, and an elevation in the Th1/Th2 ratio. In vitro experiments clarified that YPF not only promoted DCs maturation and stimulated IL-12 secretion, but also reduced the generation of OX40L and the ratio of CD4⁺ IL-13⁺ T cells. Of note, these effects were associated with the DC-mediated TSLP-OX40L pathway (121).

In conclusion, CHM promotes the functionality of DCs either directly or indirectly through various signaling pathways including MAPK, TLRs, NF-κB, or JAK-STAT. Here we summarize the pathway of CHM in regulating DC function in Figure 1. Mature DCs highly express MHC I and MHC II, CD80, CD86, and pro-inflammatory factors, activating the anti-tumor immunity. Currently, the majority of studies on signaling pathways which regulated DCs functionality are focused on NF-κB, MAPK, TLR, and JAK-STAT pathways. There is a need for further exploration of new signaling pathways induced by CHM in the maturation of DCs.

CHM does not exert its enhancing effect on the anti-tumor function of DCs via a singular signaling pathway. For instance, certain herbs, such as Radix Glycyrrhizae polysaccharide, may activate the MAPK pathway while also activating the NF-κB pathway. Currently, the majority of research focus on the regulatory effects of CHM on individual signaling pathways, while there is a lack of investigation into how CHM activates multiple signaling pathways simultaneously. In the future, utilizing gene chips or proteomics may enable researchers to elucidate the primary signaling pathways through which CHM enhances the anti-tumor functions of DCs.

CHM not only exert anti-tumor effects through the previously mentioned signaling pathways but are also capable of activating specific signaling pathways that suppress immune function. Utilizing the advanced techniques of gene chips or proteomics to investigate multiple signaling pathways, it is anticipated that researchers in the future may discover CHM monomers or compounds that selectively enhanced DC functionality through a specific activating signaling pathway.