AUTHOR=Taniguchi Hirokazu , Chavan Shweta S. , Chow Andrew , Chan Joseph M. , Mukae Hiroshi , Rudin Charles M. , Sen Triparna 

TITLE=Role of CD38 in anti-tumor immunity of small cell lung cancer

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1348982

DOI=10.3389/fimmu.2024.1348982

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>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 <italic>in vivo</italic> blockade.</p></sec><sec><title>Results</title><p>In SCLC clinical samples, <italic>CD38</italic> levels were significantly correlated with the gene expression of the immunosuppressive markers <italic>FOXP3</italic>, <italic>PD-1</italic> and <italic>CTLA-4</italic>. 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.</p></sec><sec><title>Conclusion</title><p>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.</p></sec>