American Association for Cancer Research
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Supplementary Figures and Tables from Dual Relief of T-lymphocyte Proliferation and Effector Function Underlies Response to PD-1 Blockade in Epithelial Malignancies

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posted on 2023-04-04, 01:06 authored by Camille-Charlotte Balança, Clara-Maria Scarlata, Marie Michelas, Christel Devaud, Victor Sarradin, Camille Franchet, Carlos Martinez Gomez, Carlos Gomez-Roca, Marie Tosolini, Diana Heaugwane, Françoise Lauzéral-Vizcaino, Lucile Mir-Mesnier, Virginie Féliu, Carine Valle, Frédéric Pont, Gwénaël Ferron, Laurence Gladieff, Stéphanie Motton, Yann Tanguy Le Gac, Agnès Dupret-Bories, Jérôme Sarini, Benjamin Vairel, Claire Illac, Aurore Siegfried-Vergnon, Eliane Mery, Jean-Jacques Fournié, Sébastien Vergez, Jean-Pierre Delord, Philippe Rochaix, Alejandra Martinez, Maha Ayyoub

Supplementary Figures S1-S10 and Tables S1-S3

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CALMIP supercomputing center

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ARTICLE ABSTRACT

Although understanding of T-cell exhaustion is widely based on mouse models, its analysis in patients with cancer could provide clues indicating tumor sensitivity to immune checkpoint blockade (ICB). Data suggest a role for costimulatory pathways, particularly CD28, in exhausted T-cell responsiveness to PD-1/PD-L1 blockade. Here, we used single-cell transcriptomic, phenotypic, and functional approaches to dissect the relation between CD8+ T-cell exhaustion, CD28 costimulation, and tumor specificity in head and neck, cervical, and ovarian cancers. We found that memory tumor–specific CD8+ T cells, but not bystander cells, sequentially express immune checkpoints once they infiltrate tumors, leading, in situ, to a functionally exhausted population. Exhausted T cells were nonetheless endowed with effector and tumor residency potential but exhibited loss of the costimulatory receptor CD28 in comparison with their circulating memory counterparts. Accordingly, PD-1 inhibition improved proliferation of circulating tumor–specific CD8+ T cells and reversed functional exhaustion of specific T cells at tumor sites. In agreement with their tumor specificity, high infiltration of tumors by exhausted cells was predictive of response to therapy and survival in ICB-treated patients with head and neck cancer. Our results showed that PD-1 blockade–mediated proliferation/reinvigoration of circulating memory T cells and local reversion of exhaustion occur concurrently to control tumors.

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