학술논문
Immunotherapy-activated T cells recruit and skew late-stage activated M1-like macrophages that are critical for therapeutic efficacy.
Document Type
Academic Journal
Author
van Elsas MJ; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.; Middelburg J; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.; Labrie C; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.; Roelands J; Department of Pathology, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.; Schaap G; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.; Sluijter M; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.; Tonea R; Department of Pathology, University of Chicago, Chicago, IL 60637, USA; Pritzker School of Molecular Engineering, Chicago, IL 60637, USA.; Ovcinnikovs V; Genmab, Utrecht 3584CT, the Netherlands.; Lloyd K; Genmab, Utrecht 3584CT, the Netherlands.; Schuurman J; Genmab, Utrecht 3584CT, the Netherlands.; Riesenfeld SJ; Pritzker School of Molecular Engineering, Chicago, IL 60637, USA.; Gajewski TF; Department of Pathology, University of Chicago, Chicago, IL 60637, USA.; de Miranda NFCC; Department of Pathology, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.; van Hall T; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.; van der Burg SH; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands. Electronic address: shvdburg@lumc.nl.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101130617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-3686 (Electronic) Linking ISSN: 15356108 NLM ISO Abbreviation: Cancer Cell Subsets: MEDLINE
Subject
Language
English
Abstract
Total tumor clearance through immunotherapy is associated with a fully coordinated innate and adaptive immune response, but knowledge on the exact contribution of each immune cell subset is limited. We show that therapy-induced intratumoral CD8 + T cells recruited and skewed late-stage activated M1-like macrophages, which were critical for effective tumor control in two different murine models of cancer immunotherapy. The activated CD8 + T cells summon these macrophages into the tumor and their close vicinity via CCR5 signaling. Exposure of non-polarized macrophages to activated T cell supernatant and tumor lysate recapitulates the late-stage activated and tumoricidal phenotype in vitro. The transcriptomic signature of these macrophages is also detected in a similar macrophage population present in human tumors and coincides with clinical response to immune checkpoint inhibitors. The requirement of a functional co-operation between CD8 + T cells and effector macrophages for effective immunotherapy gives warning to combinations with broad macrophage-targeting strategies.
Competing Interests: Declaration of interests V.O., K.L., and J.S. are (former) employees of Genmab and have ownership interests (including stock, patents, warrants, etc.). J.M., V.O., K.L., J.S., and T.v.H. are inventors on a patent (WO2022049220A2) involving the combination of CD3 bsAb therapy in combination with vaccination.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of interests V.O., K.L., and J.S. are (former) employees of Genmab and have ownership interests (including stock, patents, warrants, etc.). J.M., V.O., K.L., J.S., and T.v.H. are inventors on a patent (WO2022049220A2) involving the combination of CD3 bsAb therapy in combination with vaccination.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)