TY - JOUR

T1 - Arginase-1-based vaccination against the tumor microenvironment

T2 - the identification of an optimal T-cell epitope

AU - Martinenaite, Evelina

AU - Ahmad, Shamaila Munir

AU - Bendtsen, Simone Kloch

AU - Jørgensen, Mia Aaboe

AU - Weis-Banke, Stine Emilie

AU - Svane, Inge Marie

AU - Andersen, Mads Hald

PY - 2019

Y1 - 2019

N2 - l-arginine depletion by regulatory cells and cancer cells expressing arginase-1 (Arg-1) is a vital contributor to the immunosuppressive tumor microenvironment in patients with cancer. We have recently described the existence of pro-inflammatory effector T cells that recognize Arg-1. Hence, Arg-1-specific self-reactive T cells are a naturally occurring part of the memory T-cell repertoire of the human immune system. Here, we further characterize a highly immunogenic epitope from Arg-1. We describe frequent T-cell-based immune responses against this epitope in patients with cancer, as well as in healthy donors. Furthermore, we show that Arg-1-specific T cells expand in response to the TH2 cytokine interleukin (IL)-4 without any specific stimulation. Arg-1-specific memory TH1 cells that respond to increased IL-4 concentration may, therefore, drive the immune response back into the TH1 pathway. Arg-1-specific T cells thus appear to have an important function in immune regulation. Because Arg-1 plays an important role in the immunosuppressive microenvironment in most cancers, an immune modulatory vaccination approach can readily be employed to tilt the balance away from immune suppression in these settings.

AB - l-arginine depletion by regulatory cells and cancer cells expressing arginase-1 (Arg-1) is a vital contributor to the immunosuppressive tumor microenvironment in patients with cancer. We have recently described the existence of pro-inflammatory effector T cells that recognize Arg-1. Hence, Arg-1-specific self-reactive T cells are a naturally occurring part of the memory T-cell repertoire of the human immune system. Here, we further characterize a highly immunogenic epitope from Arg-1. We describe frequent T-cell-based immune responses against this epitope in patients with cancer, as well as in healthy donors. Furthermore, we show that Arg-1-specific T cells expand in response to the TH2 cytokine interleukin (IL)-4 without any specific stimulation. Arg-1-specific memory TH1 cells that respond to increased IL-4 concentration may, therefore, drive the immune response back into the TH1 pathway. Arg-1-specific T cells thus appear to have an important function in immune regulation. Because Arg-1 plays an important role in the immunosuppressive microenvironment in most cancers, an immune modulatory vaccination approach can readily be employed to tilt the balance away from immune suppression in these settings.

KW - Anti-regulatory T cells

KW - Arginase

KW - Immune-modulating vaccines

KW - IO112

KW - PIVAC 18

U2 - 10.1007/s00262-019-02425-6

DO - 10.1007/s00262-019-02425-6

M3 - Review

C2 - 31690955

AN - SCOPUS:85074775928

VL - 68

SP - 1901

EP - 1907

JO - Cancer Immunology, Immunotherapy

JF - Cancer Immunology, Immunotherapy

SN - 0340-7004

IS - 11

ER -