Contribution of resident and circulating precursors to tumor-infiltrating CD8 + T cell populations in lung cancer

Paul Gueguen (1) , Christina Metoikidou (1) , Thomas Dupic (2) , Myriam Lawand (1) , Christel Goudot (1) , Sylvain Baulande (3, 4) , Sonia Lameiras (3, 5) , Olivier Lantz (1) , Nicolas Girard (5, 6) , Agathe Seguin-Givelet (6, 7, 5, 8) , Marine Lefevre (6) , Thierry Mora (9, 10) , Aleksandra Walczak (9, 10) , Joshua Waterfall (9) , Sebastian Amigorena (1, 5)

1 U932 - Immunité et cancer
2 OEB - Department of Organismic and Evolutionary Biology [Cambridge]
3 Plateforme de génomique [Institut Curie]
4 Centre de recherche de l'Institut Curie [Paris]
5 Institut Curie [Paris]
6 IMM - Institut Mutualiste de Montsouris
7 UP13 - Université Paris 13
8 CIMI - Centre d'Immunologie et des Maladies Infectieuses
9 LPTENS - Laboratoire de Physique Théorique de l'ENS [École Normale Supérieure]
10 Physique Statistique et Inférence pour la Biologie

Tumor-infiltrating lymphocytes (TILs), in general, and especially CD8+ TILs, represent a favorable prognostic factor in non–small cell lung cancer (NSCLC). The tissue origin, regenerative capacities, and differentiation pathways of TIL subpopulations remain poorly understood. Using a combination of single-cell RNA and T cell receptor (TCR) sequencing, we investigate the functional organization of TIL populations in primary NSCLC. We identify two CD8+ TIL subpopulations expressing memory-like gene modules: one is also present in blood (circulating precursors) and the other one in juxtatumor tissue (tissue-resident precursors). In tumors, these two precursor populations converge through a unique transitional state into terminally differentiated cells, often referred to as dysfunctional or exhausted. Differentiation is associated with TCR expansion, and transition from precursor to late-differentiated states correlates with intratumor T cell cycling. These results provide a coherent working model for TIL origin, ontogeny, and functional organization in primary NSCLC

Domaines: Cancer; Immunité adaptative; Pneumologie et système respiratoire

Paul Gueguen, Christina Metoikidou, Thomas Dupic, Myriam Lawand, Christel Goudot, et al.. Contribution of resident and circulating precursors to tumor-infiltrating CD8 + T cell populations in lung cancer. Science Immunology, 2021, 6 (55), pp.eabd5778. ⟨10.1126/sciimmunol.abd5778⟩. ⟨hal-03367764⟩