TY - JOUR
T1 - The metabolic enzyme arginase-2 is a potential target for novel immune modulatory vaccines
AU - Weis-Banke, Stine Emilie
AU - Hübbe, Mie Linder
AU - Holmström, Morten Orebo
AU - Jørgensen, Mia Aaboe
AU - Bendtsen, Simone Kloch
AU - Martinenaite, Evelina
AU - Carretta, Marco
AU - Svane, Inge Marie
AU - Ødum, Niels
AU - Pedersen, Ayako Wakatsuki
AU - Met, Özcan
AU - Madsen, Daniel Hargbøl
AU - Andersen, Mads Hald
PY - 2020
Y1 - 2020
N2 - One way that tumors evade immune destruction is through tumor and stromal cell expression of arginine-degrading enzyme arginase-2 (ARG2). Here we describe the existence of pro-inflammatory effector T-cells that recognize ARG2 and can directly target tumor and tumor-infiltrating cells. Using a library of 34 peptides covering the entire ARG2 sequence, we examined reactivity toward these peptides in peripheral blood mononuclear cells from cancer patients and healthy individuals. Interferon-γ ELISPOT revealed frequent immune responses against several of the peptides, indicating that ARG2–specific self-reactive T-cells are natural components of the human T-cell repertoire. Based on this, the most immunogenic ARG2 protein region was further characterized. By identifying conditions in the microenvironment that induce ARG2 expression in myeloid cells, we showed that ARG2-specific CD4T-cells isolated and expanded from a peripheral pool from a prostate cancer patient could recognize target cells in an ARG2-dependent manner. In the ‘cold’ in vivo tumor model Lewis lung carcinoma, we found that activation of ARG2-specific T-cells by vaccination significantly inhibited tumor growth. Immune-modulatory vaccines targeting ARG2 thus are a candidate strategy for cancer immunotherapy.
AB - One way that tumors evade immune destruction is through tumor and stromal cell expression of arginine-degrading enzyme arginase-2 (ARG2). Here we describe the existence of pro-inflammatory effector T-cells that recognize ARG2 and can directly target tumor and tumor-infiltrating cells. Using a library of 34 peptides covering the entire ARG2 sequence, we examined reactivity toward these peptides in peripheral blood mononuclear cells from cancer patients and healthy individuals. Interferon-γ ELISPOT revealed frequent immune responses against several of the peptides, indicating that ARG2–specific self-reactive T-cells are natural components of the human T-cell repertoire. Based on this, the most immunogenic ARG2 protein region was further characterized. By identifying conditions in the microenvironment that induce ARG2 expression in myeloid cells, we showed that ARG2-specific CD4T-cells isolated and expanded from a peripheral pool from a prostate cancer patient could recognize target cells in an ARG2-dependent manner. In the ‘cold’ in vivo tumor model Lewis lung carcinoma, we found that activation of ARG2-specific T-cells by vaccination significantly inhibited tumor growth. Immune-modulatory vaccines targeting ARG2 thus are a candidate strategy for cancer immunotherapy.
KW - Anti-Tregs
KW - ARG2
KW - immune modulation
KW - T-win
U2 - 10.1080/2162402X.2020.1771142
DO - 10.1080/2162402X.2020.1771142
M3 - Journal article
C2 - 32923127
AN - SCOPUS:85086110849
VL - 9
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 1
M1 - 1771142
ER -