Contribution of resident and circulating precursors to tumor-infiltrating CD8 + T cell populations in lung cancer - Archive ouverte HAL
Article Dans Une Revue Science Immunology Année : 2021

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

Paul Gueguen
Christina Metoikidou
Olivier Lantz
Sebastian Amigorena
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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
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Dates et versions

hal-03367764 , version 1 (08-10-2021)

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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⟩
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