随着免疫治疗应用日渐广泛,“冷肿瘤”、“热肿瘤”等概念相继出现,那么两者之间有何区别?治疗有何差异?如何进一步提高免疫治疗疗效呢? 既往研究显示,若患者在接受免疫治疗之前,肿瘤局部或血液循环中已经存在活性较高的免疫细胞,将对后续免疫治疗发挥疗效具有重要作用。同时,免疫检查点抑制剂 (ICIs)也可引发T细胞受体(TCR)群的变化以及肿瘤反应性T细胞的特定克隆扩增[4-5]。 因此,促进T细胞募集的治疗策略或可治疗“排除型肿瘤”,目前研究亦显示,阻断β-连环蛋白信号通路等方法可募集更多T细胞,从而将“排除型肿瘤”变为“热肿瘤”,以提高免疫疗法的疗效[12]。 针对不同免疫类型肿瘤的疗法策略图 参考文献: 1. Galon, J., & Bruni, D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 18, 197-218(2019). 2. Galon, J. et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313, 1960–1964 (2006). 3. Camus, M. et al. Coordination of intratumoral immune reaction and human colorectal cancer recurrence. Cancer Res. 69, 2685–2693 (2009). 4. Bindea, G. et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 39, 782–795 (2013). 5. Wieland, A. et al. T cell receptor sequencing of activated CD8 T cells in the blood identifies tumor infiltrating clones that expand after PD-1 therapy and radiation in a melanoma patient. Cancer Immunol. Immunother. 67, 1767–1776 (2018). 6. Wolchok, J. D. et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N. Engl. J. Med. 377, 1345–1356 (2017). 7. Motzer, R. J. et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N. Engl. J. Med. 378, 1277–1290 (2018). 8. Hellmann, M. D. et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N. Engl. J. Med. 378, 2093–2104 (2018). 9. Hellmann, M. D., Friedman, C. F. & Wolchok, J. D. Combinatorial cancer immunotherapies. Adv. Immunol. 130, 251–277 (2016). 10. Buchan, S. L., Rogel, A. & Al-Shamkhani, A. The immunobiology of CD27 and OX40 and their potential as targets for cancer immunotherapy. Blood 131, 39–48 (2018). 11. Nagarsheth, N., Wicha, M. S. & Zou, W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat. Rev. Immunol. 17, 559–572 (2017). 12. Tang, H. et al. Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. Cancer Cell 29, 285–296 (2016). |
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