Upon encountering their cognate antigens, T cells can undergo clonal expansion to produce multiple copies of a cell with a shared T cell receptor (TCR). Despite the fundamental role of clonal expansion in cancer immunity, little is known about its relationship with T cell subpopulations or antitumor responses in cancer patients. Here we have performed single-cell RNA sequencing (scRNA-seq) and deep analysis of TCR clonotypes (scTCR-seq) in cancer patients across several indications, assessing the profiles of TCRs in the various populations of T cells in tumors, normal adjacent tissue (NAT), and peripheral blood. We found that, although most clonotypes were represented by a single cell, the remaining clonal lineages showed expansion in either NAT or tumor exclusively, or dual-residence with expansion in both compartments. In a subset of patients, we find clear evidence of clonotypic expansion of T effector- and effector memory-like cells not only within the tumor but also in NAT. Importantly, expanded clonotypes found in the tumor and NAT can also typically be detected in peripheral blood, suggesting a continuously replenishment from sites outside of the tumor with fresh, non-exhausted replacement cells. Our data further suggests a continued activity of the cancer immunity cycle in these patients, the acceleration of which may be associated with clinical response.

Citation Format: Shravan Madireddi, Thomas D. Wu, Patricia E. de Almeida, Romain Banchereau, Ying-Jiun J. Chen, Avantika S. Chitre, Hina Iftikhar, William E. O'Gorman, Amelia Au-Yeung, Chikara Takahashi, Leonard D. Goldstein, Chungkee Poon, Shilpa Keerthivasan, Sanjeev Mariathasan, Meghna Das Thakur, Mahrukh A. Huseni, Marcus Ballinger, Ivette Estay, Patrick Caplazi, Zora Modrusan, Lélia Delamarre, Ira Mellman, Richard Bourgon, Jane L. Grogan. Patterns of T cell clonal expansion in cancer patients associate with response to immunotherapy [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO084.