Intratumor heterogeneity: the hidden barrier to immunotherapy against MSI tumors from the perspective of IFN-γ signaling and tumor-infiltrating lymphocytes.
Intratumor heterogeneity: the hidden barrier to immunotherapy against MSI tumors from the perspective of IFN-γ signaling and tumor-infiltrating lymphocytes.
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瘤内异质性：从IFN-γ信号和肿瘤浸润淋巴细胞角度看MSI肿瘤免疫治疗的隐藏障碍
DOI：
10.1186/s13045-021-01166-3
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发表时间：
2021-10-07
影响因子：
28.5
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Wu W;Liu Y;Zeng S;Han Y;Shen H
在这个精准医疗的时代，在生物标志物的帮助下，免疫治疗显著改善了许多恶性肿瘤患者的预后。缺陷错配修复(dMMR)/微卫星不稳定性（MSI）状态在临床实践中被用作预测对免疫治疗的有利反应和预后的生物标志物。MSI是促进突变和提高对免疫治疗有利反应的可能性的重要特征。然而，许多dMMR/MSI患者对免疫治疗的反应仍然很差，部分原因是dMMR/MSI推动的肿瘤内异质性。在这篇综述中，我们讨论了dMMR/MSI如何促进肿瘤细胞的突变并产生肿瘤内异质性，特别是通过II型干扰素（IFN-γ）信号传导和肿瘤浸润淋巴细胞（TILs）。我们从dMMR/MSI、分子通路和TILs的角度探讨免疫治疗的机制，并讨论肿瘤内异质性如何阻碍免疫治疗的治疗效果。最后，我们总结了目前的技术和策略，将肿瘤作为一个整体来设计个性化的方案，并获得良好的预后。
In this era of precision medicine, with the help of biomarkers, immunotherapy has significantly improved prognosis of many patients with malignant tumor. Deficient mismatch repair (dMMR)/microsatellite instability (MSI) status is used as a biomarker in clinical practice to predict favorable response to immunotherapy and prognosis. MSI is an important characteristic which facilitates mutation and improves the likelihood of a favorable response to immunotherapy. However, many patients with dMMR/MSI still respond poorly to immunotherapies, which partly results from intratumor heterogeneity propelled by dMMR/MSI. In this review, we discuss how dMMR/MSI facilitates mutations in tumor cells and generates intratumor heterogeneity, especially through type II interferon (IFN-γ) signaling and tumor-infiltrating lymphocytes (TILs). We discuss the mechanism of immunotherapy from the perspective of dMMR/MSI, molecular pathways and TILs, and we discuss how intratumor heterogeneity hinders the therapeutic effect of immunotherapy. Finally, we summarize present techniques and strategies to look at the tumor as a whole to design personalized regimes and achieve favorable prognosis.
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影响因子：
24.5
作者：
Baker AM;Cross W;Curtius K;Al Bakir I;Choi CR;Davis HL;Temko D;Biswas S;Martinez P;Williams MJ;Lindsay JO;Feakins R;Vega R;Hayes SJ;Tomlinson IPM;McDonald SAC;Moorghen M;Silver A;East JE;Wright NA;Wang LM;Rodriguez-Justo M;Jansen M;Hart AL;Leedham SJ;Graham TA
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Graham TA
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Diehn M
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通讯作者：
Rosenberg, Steven A.
影响因子：
50.5
作者：
Burugu, S.;Gao, D.;Nielsen, T. O.
通讯作者：
Nielsen, T. O.
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4
作者：
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