RT Journal Article
T1 Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8+ T cells
A1 Matas-Rico, Elisa
A1 Moolenaar, Wouter H
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
K1 Tumores
K1 Inmunoterapia
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 CELLPRESS
YR 2021
FD 2021
LK https://hdl.handle.net/10630/32707
UL https://hdl.handle.net/10630/32707
LA eng
NO Matas-Rico, Elisa et al. Cell Reports, Volume 37, Issue 7, 110013
NO Artículo publicado en revista Cell Reports,  2021 Nov 16;37(7):110013. doi: 10.1016/j.celrep.2021.110013.
NO This work was supported by private funding to W.H.M. and grants from the Dutch Cancer Society (NKI 2013-5951 and 10764 to I.V. and NKI 2017-10894 to J.B. and I.V.), the German Research Foundation (DFG) (ME 4924/1-1 to A. Mazzocca), and the NIH (P30 GM127211 to A.J.M.). E.M.-R. is supported by a ‘‘Ramo ´n y Cajal’’ Award (RYC2019-027950-I) from Ministerio de Ciencia e Innovacio´n (MICINN), Spain.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026