Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells.
Clone Cells
Cytotoxicity, Immunologic
/ genetics
Humans
Immunotherapy
Lymphocytes, Tumor-Infiltrating
/ immunology
Melanoma
/ blood
Monitoring, Immunologic
/ methods
Neoplasm Metastasis
Phenotype
Receptors, Antigen, T-Cell, alpha-beta
/ genetics
Skin Neoplasms
/ blood
T-Lymphocytes, Cytotoxic
/ immunology
Transcriptome
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
05 04 2021
05 04 2021
Historique:
received:
07
05
2020
revised:
14
08
2020
accepted:
09
12
2020
entrez:
2
3
2021
pubmed:
3
3
2021
medline:
7
10
2021
Statut:
ppublish
Résumé
Understanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCRαβ and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell response. Paired transcriptome and TCRαβ repertoire of circulating and tumor-infiltrating T cells were analyzed at the single-cell level from matched tumor and blood from patients with metastatic melanoma. We found that in circulating T cells matching clonally expanded tumor-infiltrating T cells (circulating TILs), gene signatures of effector functions, but not terminal exhaustion, reflect those observed in the tumor. In contrast, features of exhaustion are displayed predominantly by tumor-exclusive T cells. Finally, genes associated with a high degree of blood-tumor TCR sharing were overexpressed in tumor tissue after immunotherapy. These data demonstrate that circulating TILs have unique transcriptional patterns that may have utility for the interrogation of T cell function in cancer immunotherapy.
Identifiants
pubmed: 33651881
pii: 211837
doi: 10.1084/jem.20200921
pmc: PMC7933991
pii:
doi:
Substances chimiques
Receptors, Antigen, T-Cell, alpha-beta
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : K12 CA215110
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216846
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227473
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Informations de copyright
© 2021 Lucca et al.
Déclaration de conflit d'intérêts
Disclosures: H. Kluger reported grants from Bristol-Myers Squibb, personal fees from Bristol-Myers Squibb, grants from Merck, personal fees from Merck, grants from Apexigen, personal fees from Nektar, personal fees from iovance, personal fees from Immunocore, personal fees from Celldex, personal fees from Array Biopharma, personal fees from Elevate Bio, personal fees from Instil Bio, personal fees from Clinigen, and personal fees from Shionogi outside the submitted work. D.A. Hafler had received research funding from Bristol-Myers Squibb, Sanofi, and Genentech for work unrelated to this project. He has been a consultant over the past 10 years for Bristol-Myers Squibb, Compass Therapeutics, EMD Serono, Genentech, Juno Therapeutics, Novartis Pharmaceuticals, Proclara Biosciences, Sage Therapeutics, and Sanofi Genzyme. No other disclosures were reported.
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