Myeloid-T cell interplay and cell state transitions associated with checkpoint inhibitor response in melanoma.
T cell
Translation to patients
cancer immunotherapy
immune checkpoint
macrophage
melanoma
peripheral blood mononuclear cell
single-cell RNA sequencing
tumor microenvironment
tumor-infiltrated lymphocyte
Journal
Med (New York, N.Y.)
ISSN: 2666-6340
Titre abrégé: Med
Pays: United States
ID NLM: 101769215
Informations de publication
Date de publication:
04 Apr 2024
04 Apr 2024
Historique:
received:
14
06
2023
revised:
23
11
2023
accepted:
17
03
2024
medline:
10
4
2024
pubmed:
10
4
2024
entrez:
9
4
2024
Statut:
aheadofprint
Résumé
The treatment of melanoma, the deadliest form of skin cancer, has greatly benefited from immunotherapy. However, many patients do not show a durable response, which is only partially explained by known resistance mechanisms. We performed single-cell RNA sequencing of tumor immune infiltrates and matched peripheral blood mononuclear cells of 22 checkpoint inhibitor (CPI)-naive stage III-IV metastatic melanoma patients. After sample collection, the same patients received CPI treatment, and their response was assessed. CPI responders showed high levels of classical monocytes in peripheral blood, which preferentially transitioned toward CXCL9-expressing macrophages in tumors. Trajectories of tumor-infiltrating CD8 Our study illustrates that the tumor immune microenvironment prior to CPI treatment can be indicative of response. In perspective, modulating the myeloid and/or effector cell compartment by altering the described cell interactions and transitions could improve immunotherapy response. This research was funded by Roche Pharma Research and Early Development.
Sections du résumé
BACKGROUND
BACKGROUND
The treatment of melanoma, the deadliest form of skin cancer, has greatly benefited from immunotherapy. However, many patients do not show a durable response, which is only partially explained by known resistance mechanisms.
METHODS
METHODS
We performed single-cell RNA sequencing of tumor immune infiltrates and matched peripheral blood mononuclear cells of 22 checkpoint inhibitor (CPI)-naive stage III-IV metastatic melanoma patients. After sample collection, the same patients received CPI treatment, and their response was assessed.
FINDINGS
RESULTS
CPI responders showed high levels of classical monocytes in peripheral blood, which preferentially transitioned toward CXCL9-expressing macrophages in tumors. Trajectories of tumor-infiltrating CD8
CONCLUSIONS
CONCLUSIONS
Our study illustrates that the tumor immune microenvironment prior to CPI treatment can be indicative of response. In perspective, modulating the myeloid and/or effector cell compartment by altering the described cell interactions and transitions could improve immunotherapy response.
FUNDING
BACKGROUND
This research was funded by Roche Pharma Research and Early Development.
Identifiants
pubmed: 38593812
pii: S2666-6340(24)00127-2
doi: 10.1016/j.medj.2024.03.015
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests R.S., S. Hoves, M.B., T.H., S.D., E.Y., F.L., S. Herter, P.U., A.I., J.S., J.S.-P., T.K.-T., I.G.d.M., and P.C.S. are employed by and hold F. Hoffmann-La Roche Ltd. company stock. P.U. and M.B. disclose ownership of F. Hoffmann-La Roche Ltd. patents. R.D. has intermittent, project-focused consulting and/or advisory relationships with Novartis, Merck Sharp & Dohme (MSD), Bristol-Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA, Pfizer, and touchIME outside of the submitted work. M.P.L. receives project-specific research support outside of the scope of this work from Roche, Novartis, Molecular Partners, and Oncobit.