VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML

Wang, Liru; Jia, Bei; Claxton, David F.; Ehmann, W. Christopher; Rybka, Witold B.; Mineishi, Shin; Naik, Seema; Khawaja, Muhammad Rizwan; Sivik, Jeffrey; Han, Junyan; Hohl, Raymond J.; Zheng, Hong

doi:10.1080/2162402x.2018.1469594

Cited by 130 publications

(110 citation statements)

References 41 publications

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“…We also found that normal human organs other than lymphoid tissues and placental trophoblastic cells did not express VISTA at the protein level [13]. Although VISTA protein has been detected in gastric cancer, oral squamous cell carcinoma, NSCLC, colorectal carcinoma, hepatocellular carcinoma, endometrial cancer, ovarian cancer, melanoma, and gestational trophoblastic neoplasia, its expression and relationship with patient survival vary according to the type of cancer [13][14][15][16][17][18][19][20][21]. While VISTA was mainly expressed by tumor-infiltrating lymphocytes, it was only present in 8.8% of gastric cancer cells and in 19.4-22.8% of NSCLC lesions [15,16].…”

Section: Discussionmentioning

confidence: 76%

“…These studies suggest that VISTA may modulate a novel immune evasion mechanism and is thus a potential target for cancer immunotherapy. VISTA expression in human cancers has been reported in non-small cell lung cancer (NSCLC), hepatocellular carcinoma, colorectal carcinoma, oral squamous cell carcinoma, gastric carcinoma, acute myeloid leukemia, and gestational trophoblastic neoplasia [13][14][15][16][17][18][19][20][21]. Mulati et al also found that VISTA was highly expressed in human ovarian and endometrial cancers [20].…”

Section: Introductionmentioning

confidence: 98%

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VISTA expression is associated with a favorable prognosis in patients with high-grade serous ovarian cancer

Zong

Zhou

Zhang

et al. 2019

Cancer Immunol Immunother

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Blockading programmed death ligand 1 (PD-L1) shows promising results in patients with some cancers, but not in those with ovarian cancer. V-domain Ig suppressor of T cell activation (VISTA) is a recently discovered immune checkpoint protein that suppresses T cell activation. This study aimed to investigate the expression and clinical significance of VISTA in ovarian cancer as well as its relationship with PD-L1. VISTA and PD-L1 levels in 146 ovarian cancer samples were assessed using immunohistochemistry. We investigated the association between VISTA and other clinicopathological variables, including survival. The associations between the VISTA-encoding C10orf54 gene, other immune checkpoints, and survival were analyzed. VISTA was detected in 51.4% of all samples and 46.6% of PD-L1-negative samples; it was expressed in 28.8%, 35.6%, and 4.1% of tumor cells (TCs), immune cells (ICs), and endothelial cells, respectively. Furthermore, VISTA expression was associated with pathologic type and PD-L1 expression. Moreover, VISTA expression in TCs, but not in ICs, was associated with prolonged progression-free and overall survival in patients with high-grade serous ovarian cancer. The expression of C10orf54 mRNA was associated with prolonged overall survival and immune escape-modulating genes. These results showed that VISTA expression in ovarian tumor cells was associated with a favorable prognosis in patients with high-grade serous ovarian cancer; however, additional studies are required to better understand the expression and role of VISTA in ovarian cancer. Keywords Ovarian cancer • PD-L1 • VISTA • Immune checkpoints • Prognosis Abbreviations CTLA4 Cytotoxic T-lymphocyte-associated protein 4 FIGO International federation of gynecology and obstetrics HGSOC High-grade serous ovarian carcinoma IC Immune cell LAG3 Lymphocyte activation gene-3 TCGA The cancer genome atlas TC Tumor cell TIGIT T cell immunoreceptor with Ig and ITIM domains TIM-3 T cell immunoglobulin and mucin domain-3 TMA Tumor tissue microarray VISTA V-domain Ig suppressor of T cell activation Electronic supplementary material The online version of this article (

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 98%

VISTA expression is associated with a favorable prognosis in patients with high-grade serous ovarian cancer

Zong

Zhou

Zhang

et al. 2019

Cancer Immunol Immunother

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“…In VISTA‐deficient mice, B16‐OVA melanoma and CT26 colon cancer tumors grow with reduced kinetics , and VISTA‐deficient mice also show reduced susceptibility to GL261 glioma, particularly when undergoing radiation therapy . Cells mediating VISTA suppression may be of both the T cell and myeloid lineages . Myeloid‐derived suppressor cells (MDSC) from an LP‐BM5 virus model showed a significant dependence on VISTA for suppressive function .…”

Section: The Promise Of Vista In Cancer Immunotherapymentioning

confidence: 99%

VISTA: Coming of age as a multi-lineage immune checkpoint

ElTanbouly

Schaafsma

Noelle

et al. 2020

Clinical and Experimental Immunology

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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.

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“…An expansion in the number of MDSCs has been reported in AML patients, where they inhibit T cell responses (53)(54)(55)(56). Expansion of MDSC decreases CAR T cell efficacy in solid tumors (57), and interventions that aim to inhibit MDSC function have had preclinical success in improving CAR T cell function (58).…”

Section: Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

A Bump in the Road: How the Hostile AML Microenvironment Affects CAR T Cell Therapy

Epperly

Velasquez

2020

Front. Oncol.

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Chimeric antigen receptor (CAR) T cells targeting CD19 have been successful treating patients with relapsed/refractory B cell acute lymphoblastic leukemia (ALL) and B cell lymphomas. However, relapse after CAR T cell therapy is still a challenge. In addition, preclinical and early clinical studies targeting acute myeloid leukemia (AML) have not been as successful. This can be attributed in part to the presence of an AML microenvironment that has a dampening effect on the antitumor activity of CAR T cells. The AML microenvironment includes cellular interactions, soluble environmental factors, and structural components. Suppressive immune cells including myeloid derived suppressor cells and regulatory T cells are known to inhibit T cell function. Environmental factors contributing to T cell exhaustion, including immune checkpoints, anti-inflammatory cytokines, chemokines, and metabolic alterations, impact T cell activity, persistence, and localization. Lastly, structural factors of the bone marrow niche, secondary lymphoid organs, and extramedullary sites provide opportunities for CAR T cell evasion by AML blasts, contributing to treatment resistance and relapse. In this review we discuss the effect of the AML microenvironment on CAR T cell function. We highlight opportunities to enhance CAR T cell efficacy for AML through manipulating, targeting, and evading the anti-inflammatory leukemic microenvironment.

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VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML

Cited by 130 publications

References 41 publications

VISTA expression is associated with a favorable prognosis in patients with high-grade serous ovarian cancer

VISTA expression is associated with a favorable prognosis in patients with high-grade serous ovarian cancer

VISTA: Coming of age as a multi-lineage immune checkpoint

A Bump in the Road: How the Hostile AML Microenvironment Affects CAR T Cell Therapy

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