The Expression Pattern and Clinical Significance of the Immune Checkpoint Regulator VISTA in Human Breast Cancer.
The Expression Pattern and Clinical Significance of the Immune Checkpoint Regulator VISTA in Human Breast Cancer.
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免疫检查点调节因子 VISTA 在人类乳腺癌中的表达模式和临床意义。
DOI：
10.3389/fimmu.2020.563044
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发表时间：
2020
影响因子：
7.3
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Xie X;Zhang J;Shi Z;Liu W;Hu X;Qie C;Chen W;Wang Y;Wang L;Jiang J;Liu J
针对CTLA-4和PD-1的免疫疗法已经在各种癌症中引起了有希望的反应。然而，相对较低的应答率需要确定额外的免疫抑制途径。T细胞活化的V区免疫球蛋白抑制因子(VistA)在抗肿瘤免疫中发挥重要作用，是肿瘤免疫治疗的重要靶点。在这里，我们使用单细胞RNA-seq分析了来自乳腺癌样本的14897个细胞及其配对的7,320个正常细胞的基因表达水平。然后，我们用免疫组织化学和定量免疫荧光(QIF)方法验证了免疫检查点分子(VistA、PD-1、PD-L1、TIGIT、TIM3和LAG3)在324例乳腺癌组织中的蛋白表达。单细胞RNA-SEQ结果显示，乳腺癌组织中免疫检查点VistA的表达水平高于邻近正常组织。我们还发现，VistA在乳腺癌组织中的表达水平高于其他免疫检查点。免疫组织化学结果显示，Vista在瘤内免疫细胞和乳腺癌细胞中呈膜/胞浆染色。经卡方检验或Fisher‘s检验，Vista与病理分级、淋巴结状态、PD-1水平呈正相关。此外，VistA在CD68+肿瘤相关巨噬细胞(TAMs)中的表达高于CD4+T细胞、CD8+细胞毒性T细胞或CD20+B细胞。因此，这些发现支持Vista在乳腺癌中的免疫调节作用，并表明靶向Vista可能有助于乳腺癌的免疫治疗。
Immunotherapies targeting CTLA-4 and PD-1 have elicited promising responses in a variety of cancers. However, the relatively low response rates warrant the identification of additional immunosuppressive pathways. V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitumor immunity and is a valuable target in cancer immunotherapy. Here, we used single-cell RNA-seq to analyze the gene expression levels of 14897 cells from a breast cancer sample and its paired 7,320 normal cells. Then, we validated the protein expression of immune checkpoint molecules (VISTA, PD-1, PD-L1, TIGIT, TIM3, and LAG3) in 324 human breast cancer samples by immunohistochemistry and quantitative immunofluorescence (QIF) approaches. Single cell RNA-seq results show a higher level of immune checkpoint VISTA expression in breast cancer tissue compared to adjacent normal tissue. We also found that VISTA expressed highest in breast cancer tissue than other immune-checkpoints. Immunohistochemical results showed that VISTA was detected with a membranous/cytoplasmic staining pattern in intratumoral immune cells and breast cancer cells. Additionally, VISTA was positively correlated with pathological grade, lymph node status and the levels of PD-1 according to the chi-square test or Fisher’s test. Furthermore, VISTA expression was higher in CD68+ tumor-associated macrophages (TAMs) than in CD4+ T cells, CD8+ cytotoxic T cells or CD20+ B cells. These findings therefore support the immunoregulatory role of VISTA in breast cancer and indicate that targeting VISTA may benefit breast cancer immunotherapy.
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影响因子：
11.2
作者：
Le Mercier I;Chen W;Lines JL;Day M;Li J;Sergent P;Noelle RJ;Wang L
通讯作者：
Wang L
DOI：
10.1158/1078-0432.ccr-17-2542
发表时间：
2018-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Villarroel-Espindola F;Yu X;Datar I;Mani N;Sanmamed M;Velcheti V;Syrigos K;Toki M;Zhao H;Chen L;Herbst RS;Schalper KA
通讯作者：
Schalper KA
DOI：
10.1084/jem.20100619
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Wang L;Rubinstein R;Lines JL;Wasiuk A;Ahonen C;Guo Y;Lu LF;Gondek D;Wang Y;Fava RA;Fiser A;Almo S;Noelle RJ
通讯作者：
Noelle RJ
影响因子：
82.9
作者：
Gao J;Ward JF;Pettaway CA;Shi LZ;Subudhi SK;Vence LM;Zhao H;Chen J;Chen H;Efstathiou E;Troncoso P;Allison JP;Logothetis CJ;Wistuba II;Sepulveda MA;Sun J;Wargo J;Blando J;Sharma P
通讯作者：
Sharma P
影响因子：
2.9
作者：
Liao H;Zhu H;Liu S;Wang H
通讯作者：
Wang H