Abstract
Abstract Human clear cell renal cell carcinoma (ccRCC) is one of the most immunologically distinct tumor types due to high levels of tumor-infiltrating immune cells including T cells, yet not every patient responds to immunotherapy. Interestingly, in contrast to other cancers, infiltration with cytotoxic CD8+ T cells is associated with poorer overall survival in ccRCC, suggesting that subpopulations of CD8+ and other immune cells may underlie this observation. To characterize the tumor immune microenvironment of ccRCC, we applied single-cell RNA sequencing along with T-cell receptor sequencing to map the transcriptomic heterogeneity of 25,688 individual CD45+ lymphoid and myeloid cells in matched tumor and blood from patients with ccRCC. We identified multiple and distinct immune cell phenotypes for B and T (CD4 and CD8) lymphocytes, natural kill (NK) cells, and myeloid cells. Evaluation of T-cell receptor (TCR) sequences revealed limited shared clonotypes between patients, whereas tumor-infiltrating T-cell clonotypes were frequently found in peripheral blood, albeit in lower abundance. Evaluation of myeloid subsets revealed unique gene programs defining monocytes, dendritic cells, and tumor-associated macrophages. In summary, here we have leveraged scRNA-seq to refine our understanding of the relative abundance, diversity, and complexity of the immune landscape of ccRCC. This report represents the first such characterization of the ccRCC immune landscape using scRNA-seq. With further characterization and functional validation, these findings may identify novel subpopulations of immune cells amenable to therapeutic intervention. Citation Format: Ajaykumar Vishwakarma, Nick Bocherding, Michael Chimenti, Purshottam Vishwakarma, Kenneth Nepple, Aliasger Salem, Russell W. Jenkins, Weizhou Zhang, Yousef Zakharia. Mapping immune landscape in clear cell renal carcinoma by single-cell genomics [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A80.
Published Version
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