{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rozalen C"],"funding":["Worldwide Cancer Research"],"pagination":["1549-1567.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12416865"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["43(8)"],"pubmed_abstract":["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<sup>+</sup> 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<sup>+</sup> tumor cells in BC metastasis and TIM3<sup>+</sup> 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."],"journal":["Cancer cell"],"pubmed_title":["TIM3&lt;sup&gt;+&lt;/sup&gt; breast cancer cells license immune evasion during micrometastasis outbreak."],"pmcid":["PMC12416865"],"funding_grant_id":["20-0156"],"pubmed_authors":["Albanell J","Coll-Manzano A","Guillen Y","Alemany A","Chacon JI","Martinez de Duenas E","Blasco-Benito S","Tzortzi P","Bigas A","Perez-Buira S","Martos T","Rozalen C","Palomeque JA","Avalle S","Brunel H","Sangrador I","Comerma L","Bermejo B","Rojo F","Celia-Terrassa T","Torren-Duran P","Dalmau M","Guerrero-Zotano A","Perez-Nunez I","Sanz-Flores M","Servitja S","Casanova-Acebes M"],"additional_accession":[]},"is_claimable":false,"name":"TIM3&lt;sup&gt;+&lt;/sup&gt; breast cancer cells license immune evasion during micrometastasis outbreak.","description":"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<sup>+</sup> 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<sup>+</sup> tumor cells in BC metastasis and TIM3<sup>+</sup> 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.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-06-02T02:44:57.572Z","creation":"2026-04-13T03:12:53.466Z"},"accession":"S-EPMC12416865","cross_references":{"pubmed":["40645187"],"doi":["10.1016/j.ccell.2025.06.015"]}}