Deciphering the transcriptomic landscape of tumor-infiltrating CD8 lymphocytes in B16 melanoma tumors with single-cell RNA-Seq

Détails

Ressource 1Télécharger: Carmona 2020.pdf (4163.52 [Ko])
Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_EDA6E7092CF7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Deciphering the transcriptomic landscape of tumor-infiltrating CD8 lymphocytes in B16 melanoma tumors with single-cell RNA-Seq
Périodique
OncoImmunology
Auteur(s)
Carmona Santiago J., Siddiqui Imran, Bilous Mariia, Held Werner, Gfeller David
ISSN
2162-4011 (Print)
ISSN-L
2162-402X
Statut éditorial
Publié
Date de publication
01/01/2020
Peer-reviewed
Oui
Volume
9
Numéro
1
Pages
1737369
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Recent studies have proposed that tumor-specific tumor-infiltrating CD8 <sup>+</sup> 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.
Mots-clé
Immunology, Immunology and Allergy, Oncology
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/04/2020 12:02
Dernière modification de la notice
18/07/2020 7:10
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