I read with great interest the comprehensive review by Tonutti et al. titled “Cancer in Connective Tissue Disease” (), which provides a timely analysis of the bidirectional relationship between malignancy and autoimmunity in connective tissue diseases (CTDs). The authors adeptly synthesize current evidence on cancer risk stratification, autoantibody profiles, and screening challenges across systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies (IIM), and Sjögren’s syndrome (SS). Their work underscores the critical need for multidisciplinary collaboration to address unmet needs in early detection and management.
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 (). Harmonizing laboratory techniques is essential to refine risk stratification and validate guidelines like the IMACS cancer-screening algorithm ().
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.
Statements
Author contributions
JC: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing.
Funding
The author(s) declare that no financial support was received for the research and/or publication of this article.
Conflict of interest
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
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.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1
TonuttiACeribelliAGremeseEColaFrancescoSDe SantisMSelmiC. Cancer in connective tissue disease. Front Immunol. (2025) 16:1571700.
2
CavazzanaIFrediMCeribelliAMordentiCFerrariFCarabelleseNet al. Testing for myositis specific autoantibodies: Comparison between line blot and immunoprecipitation assays in 57 myositis sera. J Immunol Methods. (2016) 433:1–5.
3
TangIYKChanSCWLiPHLiWLLukLTHChanDet al. Validation of the International Myositis Assessment and Clinical Studies Group guideline on cancer risk stratification. Rheumatol (Oxford). (2025) 64:2106–14.
Summary
Keywords
autoantibodies, autoimmunity, connective tissue disease (CTD), immunology, malignancy
Citation
Chen J (2025) Commentary: Cancer in connective tissue disease. Front. Immunol. 16:1641619. doi: 10.3389/fimmu.2025.1641619
Received
06 June 2025
Accepted
07 July 2025
Published
22 July 2025
Volume
16 - 2025
Edited by
Gunnar Houen, University of Copenhagen, Denmark
Reviewed by
Nicole Trier, University of Copenhagen, Denmark
Updates
Copyright
© 2025 Chen.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jiayi Chen, cjy13912736738@163.com
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.