Core Viewpoint - The study reveals that tumor-antigen-specific cytotoxic CD8+ T cells can be deployed remotely to inhibit lung metastasis of breast cancer, highlighting the importance of effector immune cell deployment in cancer treatment [3][8][11]. Group 1: Research Findings - The abundance of tumor-specific CD103+ CD8+ T cells in tumor-draining lymph nodes (TDLN) is associated with prolonged disease-free survival in breast cancer patients [8]. - CD103+ CD8+ T cells are activated in TDLN and recruited to the lungs via CCL25/CCR9 signaling, effectively suppressing tumor metastasis [8][9]. - Tumor-derived extracellular vesicles (EVs) polarize alveolar macrophages, leading to the release of CCL25 and IDO1, which can inhibit the deployment of CD103+ CD8+ T cells and promote lung metastasis [8][9]. Group 2: Implications for Cancer Treatment - Enhancing the recruitment of CD103+ CD8+ T cells or blocking IDO1 can potentially curb lung metastasis of tumors [9]. - The study emphasizes the adaptive immune system's capability to deploy remotely to protect distant organs from tumor metastasis, suggesting a potential therapeutic strategy in cancer treatment [11].

Core Viewpoint - Immune checkpoint blockade (ICB) therapies have shown promise in cancer treatment, but their effectiveness is limited to less than 25% of patients, highlighting the need for new immune checkpoints to enhance T cell responses against tumors [1][2]. Group 1: Research Findings - A study published by a team from UCLA identified the serotonin transporter (SERT) as a new immune checkpoint that inhibits antitumor immunity [2]. - Selective serotonin reuptake inhibitors (SSRIs), commonly used antidepressants, significantly enhance T cell anti-cancer capabilities and suppress tumor growth in various cancer models [2][10]. - The research demonstrated that SSRIs reduced tumor size by over 50% on average and improved the effectiveness of T cells in killing cancer cells [10]. Group 2: Mechanism of Action - SERT depletes serotonin secreted by intratumoral T cells, thereby inhibiting CD8 T cell antitumor responses [11]. - SSRIs were found to work synergistically with anti-PD-1 monoclonal antibodies, a common ICB therapy, leading to significant tumor size reduction and even complete remission in some mouse models [16]. Group 3: Clinical Implications - Approximately 20% of cancer patients are on antidepressants, primarily SSRIs, presenting an opportunity to explore their impact on cancer treatment outcomes [18]. - The potential for SSRIs to enhance the efficacy of existing cancer therapies could lead to significant advancements in cancer immunotherapy [19]. - The cost of repurposing FDA-approved drugs like SSRIs for cancer treatment is significantly lower than developing new therapies, making this approach particularly promising [19].