TIM3⁺乳腺癌细胞在微转移爆发时允许免疫逃避，这一成果由德尔玛医院研究所Toni Celià-Terrassa小组经过不懈努力而取得。2025年7月10日，国际知名学术期刊《癌细胞》发表了这一成果。

该课题组研究人员报道了在微转移主题乳腺癌（BC）转移主题模型中，T细胞免疫球蛋白和粘蛋白结构域3 （TIM3）在肿瘤细胞中的功能。TIM3在微转移中高度上调，促进存活、干性和免疫逃逸。TIM3⁺肿瘤细胞是在微转移的早期播种阶段特异性选择的。机制上，TIM3增加β-catenin/interleukin-1β (IL-1β)信号，在微转移过程中通过诱导免疫抑制性γδ T细胞和减少CD8 T细胞导致干细胞和免疫逃避。临床数据证实，BC转移中TIM3⁺肿瘤细胞增多，TIM3⁺肿瘤细胞是BC患者预后不良的生物标志物。在临床前模型中，（Neo）佐剂TIM3阻断可减少转移的发生和发生率。这些发现揭示了微转移免疫逃避的特定机制和TIM3阻断亚临床转移的潜在主题。

据悉，在转移中，微转移过程中肿瘤免疫相互作用的动力学尚不清楚。在微转移爆发为大转移之前识别其脆弱性可以揭示转移的治疗机会。

附：英文原文

Title: TIM3⁺ breast cancer cells license immune evasion during micrometastasis outbreak

Author: Catalina Rozalén, Irene Sangrador, Silvia Avalle, Sandra Blasco-Benito, Panagiota Tzortzi, María Sanz-Flores, José ángel Palomeque, Pau Torren-Duran, Mariona Dalmau, Helena Brunel, Albert Coll-Manzano, Iván Pérez-Núez, Tamara Martos, Sonia Servitja, Sandra Pérez-Buira, José Ignacio Chacón, ángel Guerrero-Zotano, Eduardo Martínez de Dueas, Yolanda Guillén, Laura Comerma, Begoa Bermejo, Anna Bigas, María Casanova-Acebes, Anna Alemany, Federico Rojo, Joan Albanell, Toni Celià-Terrassa

Issue&Volume: 2025-07-10

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+ 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.

DOI: 10.1016/j.ccell.2025.06.015

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00265-X