TIM3+ breast cancer cells license immune evasion during micrometastasis outbreak

In metastasis, the dynamics of tumor-immune interactions during micrometastasis remain unclear. Identifying the vulnerabilities of micrometastases before outbreaking into macrometastases can reveal therapeutic opportunities for metastasis. Here, we report a function of T cell immunoglobulin and muci...

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Detalles Bibliográficos
Autores: Rozalén, Catalina, Sangrador, Irene, Avalle, Silvia, Blasco-Benito, Sandra, Tzortzi, Panagiota, Sanz-Flores, María, Palomeque, José Ángel, Torren-Duran, Pau, Dalmau, Mariona, Brunel, Helena, Coll-Manzano, Albert, Pérez-Núñez, Iván, Martos, Tamara, Servitja Tormo, Sonia, Guillén, Yolanda, Comerma Blesa, Laura, 1983-, Bigas Salvans, Anna, Albanell Mestres, Joan, Celià-Terrassa, Toni
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:dnet:recercat____::71b26346c392c0de795adf5589c00073
Acceso en línea:https://hdl.handle.net/10230/72968
http://dx.doi.org/10.1016/j.ccell.2025.06.015
Access Level:acceso abierto
Palabra clave:EMT
TIM3
TIM3 blockade
Breast cancer
Cancer immunoediting
Immune-evasion
Metastasis
Micrometastasis
Stemness
γδ T cells
Descripción
Sumario:In metastasis, the dynamics of tumor-immune interactions during micrometastasis remain unclear. Identifying the vulnerabilities of micrometastases before outbreaking into macrometastases can reveal therapeutic opportunities for metastasis. Here, we report a function of T cell immunoglobulin and mucin domain 3 (TIM3) in tumor cells during micrometastasis using breast cancer (BC) metastasis mouse models. TIM3 is highly upregulated in micrometastases, promoting survival, stemness, and immune escape. TIM3+ tumor cells are specifically selected during early seeding of micrometastasis. Mechanistically, TIM3 increases β-catenin/interleukin-1β (IL-1β) signaling, leading to stemness and immune-evasion by inducing immunosuppressive γδ T cells and reducing CD8 T cells during micrometastasis. Clinical data confirm increased TIM3+ tumor cells in BC metastasis and TIM3+ tumor cells as a biomarker of poor outcome in BC patients. (Neo)adjuvant TIM3 blockade reduces the metastatic seeding and incidence in preclinical models. These findings unveil a specific mechanism of micrometastasis immune-evasion and the potential use of TIM3 blockade for subclinical metastasis.

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