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

Publié dans: Science Immunology, 2021, 6 (55), pp.eabd5778. ⟨10.1126/sciimmunol.abd5778⟩

Auteurs: Paul Gueguen, Christina Metoikidou, Thomas Dupic, Myriam Lawand, Christel Goudot, Sylvain Baulande, Sonia Lameiras, Olivier Lantz, Nicolas Girard, Agathe Seguin-Givelet, Marine Lefevre, Thierry Mora, Aleksandra Walczak, Joshua Waterfall, Sebastian Amigorena

Résumé

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

Lien vers Pubmed [PMID] – 33514641

Lien vers HAL – hal-03371449

Lien vers le DOI – 10.1126/sciimmunol.abd5778