Deciphering the transcriptomic landscape of tumor-infiltrating CD8 lymphocytes in B16 melanoma tumors with single-cell RNA-Seq
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1 janvier 2020
- doi: 10.1080/2162402x.2020.1737369
- issn: 2162-402X
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Thymus-dependent lymphocytes Thymus-derived cells T lymphocytes Thymus-dependent cellsCiter ce document
Santiago J. Carmona et al., « Deciphering the transcriptomic landscape of tumor-infiltrating CD8 lymphocytes in B16 melanoma tumors with single-cell RNA-Seq », Serveur académique Lausannois, ID : 10.1080/2162402x.2020.1737369
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Recent studies have proposed that tumor-specific tumor-infiltrating CD8 + T lymphocytes (CD8 TIL) can be classified into two main groups: "exhausted" TILs, characterized by high expression of the inhibitory receptors PD-1 and TIM-3 and lack of transcription factor 1 (Tcf1); and "memory-like" TILs, with self-renewal capacity and co-expressing Tcf1 and PD-1. However, a comprehensive definition of the heterogeneity existing within CD8 TILs has yet to be clearly established. To investigate this heterogeneity at the transcriptomic level, we performed paired single-cell RNA and TCR sequencing of CD8 T cells infiltrating B16 murine melanoma tumors, including cells of known tumor specificity. Unsupervised clustering and gene-signature analysis revealed four distinct CD8 TIL states - exhausted, memory-like, naïve and effector memory-like (EM-like) - and predicted novel markers, including Ly6C for the EM-like cells, that were validated by flow cytometry. Tumor-specific PMEL T cells were predominantly found within the exhausted and memory-like states but also within the EM-like state. Further, T cell receptor sequencing revealed a large clonal expansion of exhausted, memory-like and EM-like cells with partial clonal relatedness between them. Finally, meta-analyses of public bulk and single-cell RNA-seq data suggested that anti-PD-1 treatment induces the expansion of EM-like cells. Our reference map of the transcriptomic landscape of murine CD8 TILs will help interpreting future bulk and single-cell transcriptomic studies and may guide the analysis of CD8IL subpopulations in response to therapeutic interventions.