| Literature DB >> 33861994 |
Chirag Krishna1, Renzo G DiNatale2, Fengshen Kuo3, Raghvendra M Srivastava3, Lynda Vuong4, Diego Chowell4, Sounak Gupta5, Chad Vanderbilt5, Tanaya A Purohit3, Ming Liu6, Emily Kansler7, Briana G Nixon8, Ying-Bei Chen5, Vladimir Makarov4, Kyle A Blum2, Kyrollis Attalla9, Stanley Weng9, Michael L Salmans10, Mahdi Golkaram10, Li Liu10, Shile Zhang10, Raakhee Vijayaraghavan10, Traci Pawlowski10, Victor Reuter5, Maria I Carlo11, Martin H Voss11, Jonathan Coleman9, Paul Russo9, Robert J Motzer11, Ming O Li6, Christina S Leslie12, Timothy A Chan13, A Ari Hakimi14.
Abstract
Clear cell renal cell carcinomas (ccRCCs) are highly immune infiltrated, but the effect of immune heterogeneity on clinical outcome in ccRCC has not been fully characterized. Here we perform paired single-cell RNA (scRNA) and T cell receptor (TCR) sequencing of 167,283 cells from multiple tumor regions, lymph node, normal kidney, and peripheral blood of two immune checkpoint blockade (ICB)-naïve and four ICB-treated patients to map the ccRCC immune landscape. We detect extensive heterogeneity within and between patients, with enrichment of CD8A+ tissue-resident T cells in a patient responsive to ICB and tumor-associated macrophages (TAMs) in a resistant patient. A TCR trajectory framework suggests distinct T cell differentiation pathways between patients responding and resistant to ICB. Finally, scRNA-derived signatures of tissue-resident T cells and TAMs are associated with response to ICB and targeted therapies across multiple independent cohorts. Our study establishes a multimodal interrogation of the cellular programs underlying therapeutic efficacy in ccRCC.Entities:
Keywords: TCR sequencing; immunotherapy; pathology; renal cell carcinoma; single-cell RNA-sequencing; tissue-resident; tumor-associated macrophages; tyrosine kinase inhibitors
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Year: 2021 PMID： 33861994 PMCID： PMC8268947 DOI： 10.1016/j.ccell.2021.03.007
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743