隨著免疫治療應(yīng)用日漸廣泛，“冷腫瘤”、“熱腫瘤”等概念相繼出現(xiàn)，那么兩者之間有何區(qū)別？治療有何差異？如何進(jìn)一步提高免疫治療療效呢？
既往研究顯示，若患者在接受免疫治療之前，腫瘤局部或血液循環(huán)中已經(jīng)存在活性較高的免疫細(xì)胞，將對后續(xù)免疫治療發(fā)揮療效具有重要作用。同時(shí)，免疫檢查點(diǎn)抑制劑 （ICIs）也可引發(fā)T細(xì)胞受體（TCR）群的變化以及腫瘤反應(yīng)性T細(xì)胞的特定克隆擴(kuò)增[4-5]。
因此，促進(jìn)T細(xì)胞募集的治療策略或可治療“排除型腫瘤”，目前研究亦顯示，阻斷β-連環(huán)蛋白信號(hào)通路等方法可募集更多T細(xì)胞，從而將“排除型腫瘤”變?yōu)椤盁崮[瘤”，以提高免疫療法的療效[12]。
針對不同免疫類型腫瘤的療法策略圖
參考文獻(xiàn)：
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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