Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma.
adoptive cell transfer
cancer immunotherapy
cell state
clonotype dynamics
exhaustion
expansion
melanoma
tumor engraftment
tumor reactivity
tumor-infiltrating lymphocytes
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
10 Sep 2024
10 Sep 2024
Historique:
received:
18
08
2023
revised:
12
04
2024
accepted:
22
08
2024
medline:
15
9
2024
pubmed:
15
9
2024
entrez:
14
9
2024
Statut:
aheadofprint
Résumé
Adoptive cell therapy (ACT) using in vitro expanded tumor-infiltrating lymphocytes (TILs) has inconsistent clinical responses. To better understand determinants of therapeutic success, we tracked TIL clonotypes from baseline tumors to ACT products and post-ACT blood and tumor samples in melanoma patients using single-cell RNA and T cell receptor (TCR) sequencing. Patients with clinical responses had baseline tumors enriched in tumor-reactive TILs, and these were more effectively mobilized upon in vitro expansion, yielding products enriched in tumor-specific CD8
Identifiants
pubmed: 39276771
pii: S1074-7613(24)00413-8
doi: 10.1016/j.immuni.2024.08.014
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests G.C. has received grants, research support, or has been coinvestigator in clinical trials by Bristol-Myers Squibb, Tigen Pharma, Iovance, F. Hoffmann-La Roche AG, and Boehringer Ingelheim. The Lausanne University Hospital (CHUV) has received honoraria for advisory services G.C. has provided to Genentech, AstraZeneca AG, and EVIR. G.C. has previously received royalties from the University of Pennsylvania for CAR-T cell therapy licensed to Novartis and Tmunity Therapeutics. D.D.L., S.B., A.H., and G.C. are inventors on patent applications filed by the Ludwig Institute for Cancer Research Ltd. on behalf of the University of Lausanne and the CHUV pertaining to the subject matter disclosed herein, and such patent applications have been licensed to Tigen Pharma SA. S.Z. is currently an employee of F. Hoffmann-La Roche. O.M. has consulting/advisory roles for Bristol Myers Squibb, MSD, Roche, Novartis, Amgen, Pierre Fabre, and Neracare; research grants from Bristol Myers Squibb, MSD, Amgen, and PCL; was a consultant advisor or paid speaker for Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Amgen, and Nektar; and has received research funding from Bristol Myers Squibb and Pierre Fabre and is the cofounder of a cell therapy company called Cellula.