Progressive immune dysfunction with advancing disease stage in renal cell carcinoma

Cancer Cell

Fecha de publicación: 11 de marzo de 2021

Autores: David A. Braun, Kelly Street , Kelly P. Burke, David L. Cookmeyer, Thomas Denize, Christina B. Pedersen, Satyen H. Gohil, Nicholas Schindler, Lucas Pomerance, Laure Hirsch, Ziad Bakouny, Yue Hou, Juliet Forman, Teddy Huang, Shuqiang Li, Ang Cui, Derin B. Keskin, John Steinharter, Gabrielle Bouchard, Maxine Sun, Erica M. Pimenta, Wenxin Xu, Kathleen M. Mahoney, Bradley A. McGregor, Michelle S. Hirsch, Steven L. Chang, Kenneth J. Livak, David F. McDermott, Sachet A. Shukla, Lars R. Olsen, Sabina Signoretti, Arlene H. Sharpe, Rafael A. Irizarry, Toni K. Choueiri  ,Catherine J. Wu 

DOI: https://doi.org/10.1016/j.ccell.2021.02.013

Background: The tumor immune microenvironment plays a critical role in cancer progression and response to immunotherapy in clear cell renal cell carcinoma (ccRCC), yet the composition and phenotypic states of immune cells in this tumor are incompletely characterized. We performed single-cell RNA and T cell receptor sequencing on 164,722 individual cells from tumor and adjacent non-tumor tissue in patients with ccRCC across disease stages: early, locally advanced, and advanced/metastatic. Terminally exhausted CD8⁺ T cells were enriched in metastatic disease and were restricted in T cell receptor diversity.