Department of Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Clin Exp Immunol. 2020 May;200(2):120-130. doi: 10.1111/cei.13415. Epub 2020 Feb 4.
The immune response is governed by a highly complex set of interactions among cells and mediators. T cells may be rendered dysfunctional by the presence of high levels of antigen in the absence of co-stimulation while myeloid cells may be programmed towards an immunosuppressive state that promotes cancer growth and metastasis while deterring tumor immunity. In addition, inhibitory programs driven by immune checkpoint regulators dampen anti-tumor immunity. The ideal cancer immunotherapy treatment will improve both cross-priming in the tumor microenvironment and relieve suppression by the inhibitory checkpoints. Recently, blockade of programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) has elicited impressive results, but not in all patients, so additional targets are under investigation. V-set immunoglobulin domain suppressor of T cell activation (VISTA) is a novel immunoregulatory receptor that is broadly expressed on cells of the myeloid and lymphoid lineages, and is frequently implicated as a poor prognostic indicator in multiple cancers. Importantly, antibody targeting of VISTA uniquely engages both innate and adaptive immunity. This, combined with the expression of VISTA and its non-redundant activities compared to other immune checkpoint regulators, qualifies VISTA to be a promising target for improving cancer immunotherapy.
免疫反应受细胞和介质之间高度复杂的相互作用控制。在缺乏共刺激的情况下，高水平的抗原可能会使 T 细胞功能失调，而髓样细胞可能会被编程为抑制性状态，促进癌症生长和转移，同时抑制肿瘤免疫。此外，由免疫检查点调节剂驱动的抑制程序会削弱抗肿瘤免疫。理想的癌症免疫治疗将改善肿瘤微环境中的交叉引发，并缓解抑制性检查点的抑制作用。最近，程序性细胞死亡蛋白 1（PD-1）和细胞毒性 T 淋巴细胞抗原 4（CTLA-4）的阻断已经产生了令人印象深刻的结果，但并非在所有患者中都如此，因此正在研究其他靶点。T 细胞激活的 V -set 免疫球蛋白结构域抑制剂（VISTA）是一种新型免疫调节受体，广泛表达于髓系和淋巴系细胞，在多种癌症中常被认为是预后不良的指标。重要的是，VISTA 的抗体靶向作用独特地涉及固有免疫和适应性免疫。这一点，加上 VISTA 的表达及其与其他免疫检查点调节剂相比的非冗余活性，使 VISTA 有资格成为改善癌症免疫治疗的有前途的靶点。
