Role of CD38 in anti-tumor immunity of small cell lung cancer Journal Article

   


Authors: Taniguchi, H.; Chavan, S. S.; Chow, A.; Chan, J. M.; Mukae, H.; Rudin, C. M.; Sen, T.
Article Title: Role of CD38 in anti-tumor immunity of small cell lung cancer
Abstract: Introduction: Immune checkpoint blockade (ICB) with or without chemotherapy has a very modest benefit in patients with small cell lung cancer (SCLC). SCLC tumors are characterized by high tumor mutation burden (TMB) and low PD-L1 expression. Therefore, TMB and PD-L1 do not serve as biomarkers of ICB response in SCLC. CD38, a transmembrane glycoprotein, mediates immunosuppression in non-small cell lung cancer (NSCLC). In this brief report, we highlight the potential role of CD38 as a probable biomarker of immunotherapy response in SCLC. Methods: We evaluated the role of CD38 as a determinant of tumor immune microenvironment in SCLC with bulk and single-cell transcriptomic analyses and protein assessments of clinical samples and preclinical models, including CD38 in vivo blockade. Results: In SCLC clinical samples, CD38 levels were significantly correlated with the gene expression of the immunosuppressive markers FOXP3, PD-1 and CTLA-4. CD38 expression was significantly enhanced after chemotherapy and ICB treatment in SCLC preclinical models and clinical samples. A combination of cisplatin/etoposide, ICB, and CD38 blockade delayed tumor growth compared to cisplatin/etoposide. Conclusion: Our study provides a preliminary but important direction toward exploring CD38 as a potential biomarker of ICB response and CD38 blockade as a combination strategy for chemo-immunotherapy in SCLC. Copyright © 2024 Taniguchi, Chavan, Chow, Chan, Mukae, Rudin and Sen.
Keywords: lung cancer; resistance; small cell lung cancer; immune checkpoint blockade; cd38
Journal Title: Frontiers in Immunology
Volume: 15
ISSN: 1664-3224
Publisher: Frontiers Media S.A.  
Date Published: 2024-03-12
Start Page: 1348982
Language: English
DOI: 10.3389/fimmu.2024.1348982
PROVIDER: scopus
PMCID: PMC10963403
PUBMED: 38533509
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85188533860&doi=10.3389%2ffimmu.2024.1348982&partnerID=40&md5=9036ecd9f665b7cb403ba6add2f235a8
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Source: Scopus
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MSK Authors
  1. Charles Rudin
    493 Rudin
  2. Joseph Minhow Chan
    48 Chan
  3. Shweta S Chavan
    34 Chavan
  4. Andrew Chow
    45 Chow
  5. Hirokazu Taniguchi
    30 Taniguchi
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