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Irreversible electroporation augments checkpoint immunotherapy in prostate cancer and promotes tumor antigen-specific tissue-resident memory CD8+ T cells
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Irreversible electroporation augments checkpoint immunotherapy in prostate cancer and promotes tumor antigen-specific tissue-resident memory CD8+ T cells
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Journal Article
Irreversible electroporation augments checkpoint immunotherapy in prostate cancer and promotes tumor antigen-specific tissue-resident memory CD8+ T cells
2021
Overview
Memory CD8+ T cells populate non-lymphoid tissues (NLTs) following pathogen infection, but little is known about the establishment of endogenous tumor-specific tissue-resident memory T cells (T
RM
) during cancer immunotherapy. Using a transplantable mouse model of prostate carcinoma, here we report that tumor challenge leads to expansion of naïve neoantigen-specific CD8+ T cells and formation of a small population of non-recirculating T
RM
in several NLTs. Primary tumor destruction by irreversible electroporation (IRE), followed by anti-CTLA-4 immune checkpoint inhibitor (ICI), promotes robust expansion of tumor-specific CD8+ T cells in blood, tumor, and NLTs. Parabiosis studies confirm that T
RM
establishment following dual therapy is associated with tumor remission in a subset of cases and protection from subsequent tumor challenge. Addition of anti-PD-1 following dual IRE + anti-CTLA-4 treatment blocks tumor growth in non-responsive cases. This work indicates that focal tumor destruction using IRE combined with ICI is a potent in situ tumor vaccination strategy that generates protective tumor-specific T
RM
.
Irreversible electroporation (IRE), a soft-tissue ablation technique used for tumour ablation, has been suggested to promote systemic immune responses. Here the authors show that IRE, followed by anti-CTLA-4 blockade, elicits the expansion of tumor antigen-specific CD8+ T cells and is associated with tissue residency and improved anti-tumor immune response in a preclinical model of prostate cancer.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 64/60
/ Ablation
/ Animals
/ Antigens
/ Antigens, Neoplasm - immunology
/ Antigens, Neoplasm - metabolism
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - metabolism
/ Humanities and Social Sciences
/ Humans
/ Immune checkpoint inhibitors
/ Immune Checkpoint Inhibitors - pharmacology
/ Immunologic Memory - immunology
/ Male
/ Mice
/ Prostatic Neoplasms - immunology
/ Prostatic Neoplasms - therapy
/ Science
/ Tissues
/ Tumor Microenvironment - immunology
/ Tumors
