VISTA expression on tumor-infiltrating inflammatory cells in primary cutaneous melanoma correlates with poor disease-specific survival

Kuklinski, Lawrence F.; Yan, Shaofeng; Li, Zhongze; Fisher, Jan L.; Cheng, Chao; Noelle, Randolph J.; Angeles, Christina V.; Turk, Mary Jo; Ernstoff, Marc S.

doi:10.1007/s00262-018-2169-1

Cited by 95 publications

(76 citation statements)

References 32 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: 75%

“…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: 75%

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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“…The ability of TAMs to limit the efficacy of ICB therapy has been demonstrated [43,44]. TAMs express ligand molecules for checkpoint receptors, such as PD-L1/2, CD80, CD86 and VISTA (V-domain immunoglobulin suppressor of T cell activation), and possibly others; the presence of checkpoint inhibitors different from those targeted by the currently available antibodies cancels the benefit of the therapy and maintains a state of strong immunosuppression [40,[45][46][47]. The expression of PD-L1 by TAMs results in the sequestration of anti-PD-L1 mAbs [45].…”

Section: Interaction Of Tams With Immune-checkpoint Blockade Therapymentioning

confidence: 99%

Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses

Anfray

Ummarino

Andón

et al. 2019

Cells

240

205

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: Established evidence demonstrates that tumor-infiltrating myeloid cells promote rather than stop-cancer progression. Tumor-associated macrophages (TAMs) are abundantly present at tumor sites, and here they support cancer proliferation and distant spreading, as well as contribute to an immune-suppressive milieu. Their pro-tumor activities hamper the response of cancer patients to conventional therapies, such as chemotherapy or radiotherapy, and also to immunotherapies based on checkpoint inhibition. Active research frontlines of the last years have investigated novel therapeutic strategies aimed at depleting TAMs and/or at reprogramming their tumor-promoting effects, with the goal of re-establishing a favorable immunological anti-tumor response within the tumor tissue. In recent years, numerous clinical trials have included pharmacological strategies to target TAMs alone or in combination with other therapies. This review summarizes the past and current knowledge available on experimental tumor models and human clinical studies targeting TAMs for cancer treatment.

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“…In both studies, growth differences were not observed in fully immune‐incompetent mice, indicating that VISTA expressed on tumor cells is able to impair anti‐tumor immunity. Interestingly, although initial studies showed minimal expression of VISTA on human tumor cells and suggested a predominant myeloid expression in the tumor , a number of recent studies have established that while some tumor types such as melanoma are associated with immune‐restricted VISTA expression , tumor cells can show significant expression on CD45‐negative tumor cells. This has been demonstrated in gastric cancer , ovarian cancer , colorectal cancer and primary oral squamous cell mesothelioma .…”

Section: Vista Expression In On Non‐hematopoietic Cells In Cancermentioning

confidence: 99%

“…In colon cancer, analysis of the The Cancer Genome Atlas (TGCA) database showed association of high VISTA expression with poor OS . While expression of VISTA (or PD‐1 and CTLA‐4) in cutaneous melanoma by analysis of the TGCA database showed a positive association with survival, immunohistochemistry staining (IHC) demonstrated that high VISTA expression on immune cells was associated with poor survival . In ovarian cancer, while VISTA expression was not predictive for OS, VISTA expression increased with progression, and was generally increased in advanced disease .…”

Section: Vista Expression In Tumor‐infiltrating Immune Cellsmentioning

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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VISTA expression on tumor-infiltrating inflammatory cells in primary cutaneous melanoma correlates with poor disease-specific survival

Cited by 95 publications

References 32 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

Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses

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

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