2026-04-04T02:24:37Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2071832026-03-13T19:09:07Zcom_2072_1057col_2072_478908col_2072_478917

00925njm 22002777a 4500 dc Chaib, S. author López Domínguez, J. A. author Lalinde Gutiérrez, M. author Prats, Neus author Marin, I. author Boix, O. author Garcia Garijo, A. author Meyer, K. author Muñoz, M. I. author Aguilera, M. author Mateo, L. author Stephan Otto Attolini, C. author Llanos, S. author Pérez Ramos, S. author Escorihuela, M. author Al Shahrour, F. author Cash, T. P. author Tchkonia, T. author Kirkland, J. L. author Abad, María author Gros, A. author Arribas, J. author Serrano, Manuel author 2024-02-06T11:55:29Z 2024-02-06T11:55:29Z 2024-01-24 2024-02-05T16:30:26Z Chemotherapy often generates intratumoral senescent cancer cells that strongly modify the tumor microenvironment, favoring immunosuppression and tumor growth. We discovered, through an unbiased proteomics screen, that the immune checkpoint inhibitor programmed cell death 1 ligand 2 (PD-L2) is highly upregulated upon induction of senescence in different types of cancer cells. PD-L2 is not required for cells to undergo senescence, but it is critical for senescent cells to evade the immune system and persist intratumorally. Indeed, after chemotherapy, PD-L2-deficient senescent cancer cells are rapidly eliminated and tumors do not produce the senescence-associated chemokines CXCL1 and CXCL2. Accordingly, PD-L2-deficient pancreatic tumors fail to recruit myeloid-derived suppressor cells and undergo regression driven by CD8 T cells after chemotherapy. Finally, antibody-mediated blockade of PD-L2 strongly synergizes with chemotherapy causing remission of mammary tumors in mice. The combination of chemotherapy with anti-PD-L2 provides a therapeutic strategy that exploits vulnerabilities arising from therapy-induced senescence. © 2024, The Author(s). Quimioteràpia Cèl·lules canceroses Chemotherapy Cancer cells The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2