Rules of Engagement: The Lymphocyte Receptor Ecosystem in Renal Cell Carcinoma.

ABSTRACT

Immune receptor repertoires provide insight into the clonal distribution of tumor-infiltrating lymphocytes, yet the clinical implications of T-cell receptor (TCR) and B-cell receptor (BCR) repertoire diversity in cancer are unclear. In this issue of Cancer Research, Ferral-Fairbanks and colleagues reveal the interplay between repertoire diversity, tumor molecular features, and clinical outcome in renal cell carcinoma (RCC). The authors show that aggressive tumors harbor increasingly diverse TCR and BCR repertoires and that both repertoires are altered by common RCC driver mutations. Moreover, the authors demonstrate that high TCR diversity is associated with improved overall survival. This study highlights the contribution of lymphocyte receptor dynamics to the emerging complexity of RCC antitumor immune responses. See related article by Ferral-Fairbanks et al., p. 929.