In vivo study of the Tim3-loss in breast cancer cells during metastasis

In metastasis, the existence tumor cells overcoming the immune system during early organ seeding is crucial, yet the dynamics of tumor-immune interactions during micrometastasis remain unclear. Examining the immune selective pressure in breast cancer (BC) mouse models, we unexpectedly found TIM3 among the most upregulated genes in metastatic surviving BC cells. The selection of TIM3+ tumor cells, was specifically occurring during early seeding of micrometastasis, escaping the immune attack and acquiring stemness. Also clinical data confirmed increased TIM3+ tumor cells in BC metastasis. The aim of the study was to understand the mechanistic insgihts of Tim3 in breast cancer cells in vivo to decipher pivotal pathways of Tim3-mediated immun-evasion. Overall design: To evaluate Tim3 during metastasis in vivo, Ctrl and Tim3-KD 4TO7 cells were implanted via intracardiac injection in Balb/c mice. After metastatic colonization, lung and liver were extracted for transcriptomic interrogation of tumor cells.