Edited by: Gunnar Houen, University of Copenhagen, Denmark
Reviewed by: Nicole Trier, University of Copenhagen, Denmark
*Correspondence: Jiayi Chen,
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I read with great interest the comprehensive review by Tonutti et al. titled “Cancer in Connective Tissue Disease” (
I commend the authors for highlighting the paradoxical role of autoimmunity—where chronic inflammation may promote oncogenesis, yet autoimmune responses can also exert antitumor effects. This duality is exemplified by the contrasting implications of autoantibodies like anti-TIF1-γ (high cancer risk in IIM) and anti-Sp4/CCAR1 (potentially protective). However, I emphasize the urgent need for standardized autoantibody detection methods. As noted, discrepancies in anti-NXP2 results across assays (e.g., line blot vs. immunoprecipitation) complicate clinical interpretation (
I also support the call for disease-specific screening frameworks. While IMACS offers a model for IIM, similar protocols are lacking for systemic sclerosis and Sjögren’s syndrome, where lymphoma risk escalates with biomarkers like ectopic germinal centers or CXCL13. Tailored strategies must integrate serological, clinical, and imaging data (e.g., salivary gland ultrasound in SS) while balancing cost-effectiveness and accessibility.
Finally, the impact of immunosuppressants on cancer risk warrants deeper exploration. Although the review notes inconclusive data on therapies like mycophenolate in systemic sclerosis, real-world studies are needed to clarify risks associated with newer biologics (e.g., rituximab) and the potential protective role of hydroxychloroquine. Pharmacovigilance registries could illuminate these associations.
In conclusion, Tonutti et al. have delivered an invaluable review that crystallizes the complex cancer-CTD interplay. Future efforts should prioritize validating autoantibody panels, expanding screening guidelines, and elucidating treatment-related oncogenic risks through international cohorts.
JC: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing.
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The author(s) declare that Generative AI was used in the creation of this manuscript. The author would like to thank Deepseek for its assistance in the preparation of this letter.
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