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Chow, Andrew; Uddin, Fathema Z.; Liu, Michael; Dobrin, Anton; Nabet, Barzin Y.; Mangarin, Levi; Lavin, Yonit; Rizvi, Hira; Tischfield, Sam E.; Quintanal-Villalonga, Alvaro; Chan, Joseph M.; Shah, Nisargbhai; Allaj, Viola; Manoj, Parvathy; Mattar, Marissa; Meneses, Maximiliano; Landau, Rebecca; Ward, Mariana; Kulick, Amanda; Kwong, Charlene; Wierzbicki, Matthew; Yavner, Jessica; Egger, Jacklynn; Chavan, Shweta S.; Farillas, Abigail; Holland, Aliya; Sridhar, Harsha; Ciampricotti, Metamia; Hirschhorn, Daniel; Guan, Xiangnan; Richards, Allison L.; Heller, Glenn; Mansilla-Soto, Jorge; Sadelain, Michel; Klebanoff, Christopher A.; Hellmann, Matthew D.; Sen, Triparna; de Stanchina, Elisa; Wolchok, Jedd D.; Merghoub, Taha; Rudin, Charles M.
Immunity (Cambridge, Mass.), 01/2023, Letnik: 56, Številka: 1Journal Article
Improved identification of anti-tumor T cells is needed to advance cancer immunotherapies. CD39 expression is a promising surrogate of tumor-reactive CD8+ T cells. Here, we comprehensively profiled CD39 expression in human lung cancer. CD39 expression enriched for CD8+ T cells with features of exhaustion, tumor reactivity, and clonal expansion. Flow cytometry of 440 lung cancer biospecimens revealed weak association between CD39+ CD8+ T cells and tumoral features, such as programmed death-ligand 1 (PD-L1), tumor mutation burden, and driver mutations. Immune checkpoint blockade (ICB), but not cytotoxic chemotherapy, increased intratumoral CD39+ CD8+ T cells. Higher baseline frequency of CD39+ CD8+ T cells conferred improved clinical outcomes from ICB therapy. Furthermore, a gene signature of CD39+ CD8+ T cells predicted benefit from ICB, but not chemotherapy, in a phase III clinical trial of non-small cell lung cancer. These findings highlight CD39 as a proxy of tumor-reactive CD8+ T cells in human lung cancer. •CD39+ CD8+ T cells express features of exhaustion and tumor reactivity•CD39 expression enriches for CD8+ TCRs with tumor reactivity•CD39 expression on CD8+ T cells is non-redundant to tumor-based biomarkers•CD39+ CD8+ T cells are predictive of benefit from ICB Factors predicting benefit of immune checkpoint blockade (ICB) are needed. Here, Chow et al. demonstrate that CD39 expression marks tumor-reactive CD8+ T cells. High baseline levels of CD39+ CD8+ T cells are associated with ICB efficacy in lung cancer. Thus, CD39 is a potential tumor-extrinsic biomarker for guiding cancer management.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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