美国丹娜-法伯癌症研究所Catherine J. Wu研究小组取得一项新突破。他们的最新研究揭示了免疫功能紊乱与进展期肾细胞癌的关系。相关论文在线发表在2021年3月11日出版的《癌细胞》杂志上。
Title: Progressive immune dysfunction with advancing disease stage in renal cell carcinoma
Author: 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
Abstract: The tumor immune microenvironment plays a critical role in cancer progression andresponse to immunotherapy in clear cell renal cell carcinoma (ccRCC), yet the compositionand phenotypic states of immune cells in this tumor are incompletely characterized.We performed single-cell RNA and T cell receptor sequencing on 164,722 individualcells from tumor and adjacent non-tumor tissue in patients with ccRCC across diseasestages: early, locally advanced, and advanced/metastatic. Terminally exhausted CD8+ T cells were enriched in metastatic disease and were restricted in T cell receptordiversity. Within the myeloid compartment, pro-inflammatory macrophages were decreased,and suppressive M2-like macrophages were increased in advanced disease. Terminallyexhausted CD8+ T cells and M2-like macrophages co-occurred in advanced disease and expressed ligandsand receptors that support T cell dysfunction and M2-like polarization. This immunedysfunction circuit is associated with a worse prognosis in external cohorts and identifiespotentially targetable immune inhibitory pathways in ccRCC.