Expression of the immune checkpoint VISTA in breast cancer

Zong, Liju; Mo, Shengwei; Yu, Shuangni; Zhou, Yuan; Zhang, Ming; Chen, Jie; Xiang, Yang

doi:10.1007/s00262-020-02554-3

Cited by 54 publications

(56 citation statements)

References 37 publications

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“…This study evaluated VISTA expression in a large cohort of human breast cancer patients. Recently, a newly published study also used immunohistochemistry to study the expression of VISTA in 919 cases of ductal carcinoma, and found that the expression of VISTA on immune cells was associated with a favorable prognosis (27). Consistent with the study, our data showed that VISTA was expressed in a substantial number of immune cells.…”

Section: Discussionsupporting

confidence: 88%

The Expression Pattern and Clinical Significance of the Immune Checkpoint Regulator VISTA in Human Breast Cancer

et al. 2020

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Background: 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. Methods: 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. Results: 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. Conclusions: 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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Section: Discussionsupporting

confidence: 88%

The Expression Pattern and Clinical Significance of the Immune Checkpoint Regulator VISTA in Human Breast Cancer

et al. 2020

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“…We dichotomized the VISTA expression in TCs and ICs into “negative” and “positive” groups, according to the median of raw proportion values. The median value of VISTA expression in ICs was 5%, which was consistent with the cutoff values recommended in previous studies ( 28 , 29 ), while expression in tumor cells was 0%.…”

Section: Methodssupporting

confidence: 90%

“…In vitro studies on cell lines and mouse models demonstrated that VISTA was principally expressed in leukocytes infiltrating the TME ( 18 ). Zong et al ( 29 ) suggested that in BCs, the expression of VISTA in ICs was higher than that in TCs, but the overall positive rate was lower than that of this study. Studies on gastric cancer ( 34 ) and non–small cell lung cancer (NSCLC) ( 19 ) suggested that VISTA was expressed more in ICs than in TCs.…”

Section: Discussioncontrasting

confidence: 84%

“…However, the relevance of VISTA expression in the TME in survival remains controversial. In this study, TNBC patients with VISTA-positive ICs, especially the T1-2N0 stage patients and basal-like subgroup patients had a significantly favorable prognosis in terms of RFS and OS Recent studies on esophageal adenocarcinoma ( 28 ) and breast cancer ( 29 ) also confirmed that high levels of VISTA in ICs was related to a better prognosis. Research on NSCLC ( 19 ) showed that a high VISTA expression in the tumor area was related to prolonged survival, while in most cases, it was only expressed in the tumor stroma.…”

Section: Discussionsupporting

confidence: 58%

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VISTA Expression on Immune Cells Correlates With Favorable Prognosis in Patients With Triple-Negative Breast Cancer

et al. 2021

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V-domain Ig suppressor of T-cell activation (VISTA), a newly discovered negative immune checkpoint, is thought to be related to immunotherapy resistance and may become a new immune therapeutic target. Here, we evaluated the expression of VISTA in a cohort containing 254 patients with untreated triple-negative breast cancer. The relevance of VISTA expression, clinicopathologic parameters, expression of other immune markers, and prognosis were investigated in the whole cohort. Genomic analysis of 139 triple-negative breast cancer (TNBC) patients from the cancer genome atlas (TCGA) was also performed. VISTA was expressed in the immune cells (ICs) and in the tumor cells (TCs) in 87.8% (223/254) and 18.5% (47/254) of the cohort, respectively. VISTA-positive ICs were associated with no lymph node metastasis (p < 0.001), American Joint Committee on Cancer (AJCC) stage I and II (p = 0.001) and basal-like subtype (p < 0.001). VISTA expression in ICs positively correlated with some tumor-infiltrating lymphocytes (TILs) types, particularly with the CD4+TILs, which was consistent with mRNA level analysis from the TCGA database. Survival analysis showed that patients with VISTA-positive ICs had prolonged relapse-free and overall survival compared with the negative ones, especially among T1-2N0 stage patients. Multivariate analysis showed that it independently predicted the prognosis. These data confirmed the regulatory role of VISTA in anti-tumor immunity, changed our perception of VISTA as a negative immune checkpoint, and suggested VISTA as a potential therapeutic target for TNBC.

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“…In vitro studies on cell lines and mouse models demonstrated that VISTA was principally expressed in leukocytes infiltrating the TME (18). Zong et al (29) suggested that in BCs, the expression of VISTA in ICs was higher than that in TCs, but the overall positive rate was lower than that of this study. Studies on gastric cancer (34) and non-small cell lung cancer (NSCLC) (19) suggested that VISTA was expressed more in ICs than in TCs.…”

Section: Discussioncontrasting

confidence: 64%

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Expression of the immune checkpoint VISTA in breast cancer

Cited by 54 publications

References 37 publications

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

VISTA Expression on Immune Cells Correlates With Favorable Prognosis in Patients With Triple-Negative Breast Cancer

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