免疫|CD：新型細胞內免疫檢查點誕生，抗癌效果或超PD-1抑制劑( 三 ) fl|細胞|Tiganis|抗癌|研究|抑制劑

值得一提的是， Tiganis團隊還發現，PTP1B缺失或抑制也能促進CAR-T細胞的效應功能和向實體瘤的浸潤，增強CAR-T細胞對實體瘤的抑制能力。
總而言之，此項研究為腫瘤免疫治療尋找到一個新的細胞內免疫檢查點，證明靶向PTP1B可以提高CTL的殺傷功能，促進T細胞向效應或記憶表型分化，增加TIL數量。讓人眼前一亮的是，小鼠實驗表明， PTP1B抑制劑的效果優于PD-1抑制劑，而且PTP1B抑制劑聯合PD-1抑制劑還能發揮1+1＞2的效果。
在未來， PTP1B抑制劑與PD-1抑制劑聯合使用，或許能解決PD-1抑制劑的耐藥性問題，將免疫細胞浸潤少的“冷腫瘤”轉化為炎癥型的“熱腫瘤”從而更好的響應免疫治療。
此外， PTP1B這個細胞內的免疫檢查點，也有可能成為CAR-T治療實體瘤的突破口。

文章圖片

參考文獻
2. Topalian SL, Sznol M, McDermott DF, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32(10):1020-1030. doi:10.1200/JCO.2013.53.0105
3. Restifo NP, Smyth MJ, Snyder A. Acquired resistance to immunotherapy and future challenges. Nat Rev Cancer. 2016;16(2):121-126. doi:10.1038/nrc.2016.2
6. Patsoukis N, Wang Q, Strauss L, Boussiotis VA. Revisiting the PD-1 pathway. Sci Adv. 2020;6(38):eabd2712. Published 2020 Sep 18. doi:10.1126/sciadv.abd2712
9. Lantz KA, Hart SG, Planey SL, et al. Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice. Obesity (Silver Spring). 2010;18(8):1516-1523. doi:10.1038/oby.2009.444
10. Krishnan N, Koveal D, Miller DH, et al. Targeting the disordered C terminus of PTP1B with an allosteric inhibitor. Nat Chem Biol. 2014;10(7):558-566. doi:10.1038/nchembio.1528
11. Julien SG, Dubé N, Read M, et al. Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis. Nat Genet. 2007;39(3):338-346. doi:10.1038/ng1963
12. Sade-Feldman M, Yizhak K, Bjorgaard SL, et al. Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma [published correction appears in Cell. 2019 Jan 10;176(1-2):404]. Cell. 2018;175(4):998-1013.e20. doi:10.1016/j.cell.2018.10.038
【免疫|CD：新型細胞內免疫檢查點誕生，抗癌效果或超PD-1抑制劑】13. Courtney AH, Lo WL, Weiss A. TCR Signaling: Mechanisms of Initiation and Propagation. Trends Biochem Sci. 2018;43(2):108-123. doi:10.1016/j.tibs.2017.11.008