TIGIT, the Next Step Towards Successful Combination Immune Checkpoint Therapy in Cancer.
TIGIT, the Next Step Towards Successful Combination Immune Checkpoint Therapy in Cancer.
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TIGIT，癌症联合免疫检查点疗法成功的下一步。
DOI：
10.3389/fimmu.2021.699895
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发表时间：
2021
影响因子：
7.3
通讯作者：
Kwekkeboom J
中科院分区：
文献类型：
--
作者：
Ge Z;Peppelenbosch MP;Sprengers D;Kwekkeboom J
具有IG和ITIM结构域的T细胞免疫受体（TIGIT）是在几种类型的淋巴细胞上表达的抑制性受体。TIGIT抗体阻断在癌症免疫治疗中的功效目前正在临床前和临床研究中广泛研究。在多种癌症中，TIGIT在肿瘤浸润性细胞毒性T细胞、辅助T细胞、调节性T细胞和NK细胞上表达，并且其主要配体CD 155在肿瘤浸润性骨髓细胞上表达并在癌细胞上上调，这有助于免疫监视的局部抑制。虽然单一TIGIT阻断具有有限的抗肿瘤功效，但临床前研究表明TIGIT和PD-1/PD-L1途径的共阻断导致肿瘤排斥，尤其是即使在抗PD-1抗性肿瘤模型中。在抑制性免疫检查点分子中，TIGIT阻断的独特性质是其不仅增强抗肿瘤效应T细胞应答，而且增强NK细胞应答，并降低调节性T细胞的抑制能力。最近已经启动了许多关于癌症中TIGIT阻断的临床试验，主要是组合治疗。第一个中期结果显示了在实体癌患者中组合TIGIT和PD-L1共阻断的前景。在这篇综述中，我们总结了目前的知识，并确定了我们目前对TIGIT在癌症免疫中的作用的理解的差距，并根据这些见解提供了其在癌症免疫治疗中的定位建议。
T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory receptor expressed on several types of lymphocytes. Efficacy of antibody blockade of TIGIT in cancer immunotherapy is currently widely being investigated in both pre-clinical and clinical studies. In multiple cancers TIGIT is expressed on tumor-infiltrating cytotoxic T cells, helper T cells, regulatory T cells and NK cells, and its main ligand CD155 is expressed on tumor-infiltrating myeloid cells and upregulated on cancer cells, which contributes to local suppression of immune-surveillance. While single TIGIT blockade has limited anti-tumor efficacy, pre-clinical studies indicate that co-blockade of TIGIT and PD-1/PD-L1 pathway leads to tumor rejection, notably even in anti-PD-1 resistant tumor models. Among inhibitory immune checkpoint molecules, a unique property of TIGIT blockade is that it enhances not only anti-tumor effector T-cell responses, but also NK-cell responses, and reduces the suppressive capacity of regulatory T cells. Numerous clinical trials on TIGIT-blockade in cancer have recently been initiated, predominantly combination treatments. The first interim results show promise for combined TIGIT and PD-L1 co-blockade in solid cancer patients. In this review, we summarize the current knowledge and identify the gaps in our current understanding of TIGIT’s roles in cancer immunity, and provide, based on these insights, recommendations for its positioning in cancer immunotherapy.
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影响因子：
7.2
作者：
Hung AL;Maxwell R;Theodros D;Belcaid Z;Mathios D;Luksik AS;Kim E;Wu A;Xia Y;Garzon-Muvdi T;Jackson C;Ye X;Tyler B;Selby M;Korman A;Barnhart B;Park SM;Youn JI;Chowdhury T;Park CK;Brem H;Pardoll DM;Lim M
通讯作者：
Lim M
DOI：
10.1073/pnas.97.1.79
发表时间：
2000-01-04
影响因子：
11.1
作者：
He, YN;Bowman, VD;Rossmann, MG
通讯作者：
Rossmann, MG
影响因子：
29.4
作者：
Chiu, David Kung-Chun;Yuen, Vincent Wai-Hin;Wong, Carmen Chak-Lui
通讯作者：
Wong, Carmen Chak-Lui
影响因子：
20.3
作者：
Guillerey, Camille;Harjunpaeae, Heidi;Smyth, Mark J.
通讯作者：
Smyth, Mark J.
影响因子：
32.4
作者：
Gur, Chamutal;Ibrahim, Yara;Isaacson, Batya;Yamin, Rachel;Abed, Jawad;Gamliel, Moriya;Enk, Jonatan;Bar-On, Yotam;Stanietsky-Kaynan, Noah;Coppenhagen-Glazer, Shunit;Shussman, Noam;Almogy, Gideon;Cuapio, Angelica;Hofer, Erhard;Mevorach, Dror;Tabib, Adi;Ortenberg, Rona;Markel, Gal;Miklic, Karmela;Jonjic, Stipan;Brennan, Caitlin A.;Garrett, Wendy S.;Bachrach, Gilad;Mandelboim, Ofer
通讯作者：
Mandelboim, Ofer