Distinct immunological mechanisms of CTLA-4 and PD-1 blockade revealed by analyzing TCR usage in blood lymphocytes
Lidia Robert, Christina Harview, Ryan Emerson, Xiaoyan Wang, Stephen Mok, Blanca Homet, Begonya Comin-Anduix, Richard C Koya, Harlan Robins, Paul C Tumeh, Antoni Ribas, Lidia Robert, Christina Harview, Ryan Emerson, Xiaoyan Wang, Stephen Mok, Blanca Homet, Begonya Comin-Anduix, Richard C Koya, Harlan Robins, Paul C Tumeh, Antoni Ribas
Abstract
Targeting immune inhibitory receptors has brought excitement, innovation and hope to cancer patients. Our recent work revealed the immunological effects of blocking the CTLA4 and PD-1 immune checkpoints on T cell receptor usage among peripheral blood cells, and further uncovers how the expansion of the T cell repertoire matches the immunotoxicity profile of the therapy.
Keywords: CTLA-4; MK-3475; PBMC; PD-1; TCR; Tremelimumab; sequencing.
Figures
Figure 1. Immunotherapy-specific changes in the absolute number of unique T cell receptor sequences in cancer patient blood lymphocytes. Changes in the T cell receptor (TCR) usage among circulating T cells in the peripheral blood reported between baseline (day 0) and 30 to 60 d following treatment. Data shown are from 21 patients with metastatic melanoma treated with the CTLA-4 blocking antibody tremelimumab (GA, in black), nine with the PD-1 blockade agent MK-3475 (MK, in gray) and four healthy donors (HD, in white).
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Source: PubMed