2026-08-29T12:39:53Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/185032024-11-28T14:47:27Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Matas-Rico, Elisa author Frijlink, Elselien author van der Haar Àvila, Irene author Menegakis, Apostolos author van Zon, Maaike author Morris, Andrew J. author Koster, Jan author Salgado-Polo, Fernando author de Kivit, Sander author Lança, Telma author Mazzocca, Antonio author Johnson, Zoë author Haanen, John author Schumacher, Ton N. author Perrakis, Anastassis author Verbrugge, Inge author van den Berg, Joost H. author Borst, Jannie author Moolenaar, Wouter H. author 2021-11-16 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. 10.1016/j.celrep.2021.110013 2211-1247 Cell Reports http://hdl.handle.net/10668/3753 34788605 http://hdl.handle.net/20.500.12105/18503 G protein-coupled receptors T cells Anti-cancer vaccination Autotaxin Chemorepulsion Immunotherapy Iysophosphatidic acid Melanoma Single-cell RNAseq Tumor microenvironment Receptores acoplados a proteínas G Linfocitos T Inmunoterapia Microambiente tumoral Neoplasias Células Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8+ T cells