RT Journal Article
T1 Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8+ T cells
A1 Matas-Rico, Elisa
A1 Frijlink, Elselien
A1 van der Haar Àvila, Irene
A1 Menegakis, Apostolos
A1 van Zon, Maaike
A1 Morris, Andrew J.
A1 Koster, Jan
A1 Salgado-Polo, Fernando
A1 de Kivit, Sander
A1 Lança, Telma
A1 Mazzocca, Antonio
A1 Johnson, Zoë
A1 Haanen, John
A1 Schumacher, Ton N.
A1 Perrakis, Anastassis
A1 Verbrugge, Inge
A1 van den Berg, Joost H.
A1 Borst, Jannie
A1 Moolenaar, Wouter H.
K1 G protein-coupled receptors
K1 T cells
K1 Anti-cancer vaccination
K1 Autotaxin
K1 Chemorepulsion
K1 Immunotherapy
K1 Iysophosphatidic acid
K1 Melanoma
K1 Single-cell RNAseq
K1 Tumor microenvironment
K1 Receptores acoplados a proteínas G
K1 Linfocitos T
K1 Inmunoterapia
K1 Microambiente tumoral
K1 Neoplasias
K1 Células
AB Autotaxin (ATX; ENPP2) produces lysophosphatidic acid (LPA) that regulates multiple biological functions via cognate G protein-coupled receptors LPAR1-6. ATX/LPA promotes tumor cell migration and metastasis via LPAR1 and T cell motility via LPAR2, yet its actions in the tumor immune microenvironment remain unclear. Here, we show that ATX secreted by melanoma cells is chemorepulsive for tumor-infiltrating lymphocytes (TILs) and circulating CD8+ T cells ex vivo, with ATX functioning as an LPA-producing chaperone. Mechanistically, T cell repulsion predominantly involves Gα12/13-coupled LPAR6. Upon anti-cancer vaccination of tumor-bearing mice, ATX does not affect the induction of systemic T cell responses but, importantly, suppresses tumor infiltration of cytotoxic CD8+ T cells and thereby impairs tumor regression. Moreover, single-cell data from melanoma tumors are consistent with intratumoral ATX acting as a T cell repellent. These findings highlight an unexpected role for the pro-metastatic ATX-LPAR axis in suppressing CD8+ T cell infiltration to impede anti-tumor immunity, suggesting new therapeutic opportunities.
PB Cell Press
YR 2021
FD 2021-11-16
LK http://hdl.handle.net/10668/3753
UL http://hdl.handle.net/10668/3753
LA en
NO Matas-Rico E, Frijlink E, van der Haar Àvila I, Menegakis A, van Zon M, Morris AJ, et al. Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8+ T cells. Cell Rep. 2021 Nov 16;37(7):110013
DS RISalud
RD Apr 7, 2025