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Article Dans Une Revue Science Immunology Année : 2021

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

Sylvain Baulande
Nicolas Girard
Marine Lefevre
  • Fonction : Auteur

Résumé

Tumor-infiltrating lymphocytes (TILs) in general, and CD8 + TILs in particular, represent a favorable prognostic factor in non-small cell lung cancer (NSCLC). The tissue origin, regenerative capacities, and differentiation pathways of TIL subpopulations, however, 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 juxta-tumor 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, filiation and functional organization in primary NSCLC.
CD8 + T cells in lung tumors differentiate through convergent pathways to an expanded and actively cycling terminal state.
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Dates et versions

hal-02988498 , version 1 (06-11-2020)

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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 non-small cell lung cancer patients. Science Immunology, 2021, 6 (55), pp.eabd5778. ⟨10.1126/sciimmunol.abd5778⟩. ⟨hal-02988498⟩
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