Expression of VISTA correlated with immunosuppression and synergized with CD8 to predict survival in human oral squamous cell carcinoma

Wu, Lei; Deng, Wei‐Wei; Huang, Cong-Fa; Bu, Lin‐Lin; Yu, Guang‐Tao; Mao, Liang; Zhang, Wenfeng; Liu, Bing; Sun, Zhi‐Jun

doi:10.1007/s00262-017-1968-0

Cited by 139 publications

(138 citation statements)

References 39 publications

Supporting

Mentioning

131

Contrasting

Order By: Relevance

“…However, and despite seeing increased CD8 T-cell function, no effect on tumor growth was detected after treatment with the combination of anti-VISTA/PD-1 treatment in an oral squamous cell carcinoma model (22). In support of our findings in human tumors, a recent study showed a positive association between VISTA and PD-L1 protein levels; and a cooperative effect of VISTA and CD8+ cells to predict survival in a retrospective cohort of human oral squamous carcinomas (31). Taken together, these data suggest that VISTA/PD-1H pathway may contribute to the adaptive resistance mechanisms operating in tumor microenvironment.…”

Section: Discussionsupporting

confidence: 89%

Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non–Small Cell Lung Cancer

Villarroel‐Espíndola

Datar

et al. 2018

Clinical Cancer Research

172

150

View full text Add to dashboard Cite

Purpose Determine the localized expression pattern and clinical significance of VISTA/PD-1H in human NSCLC. Experimental Design Using multiplex quantitative immunofluorescence (QIF), we performed localized measurements of VISTA, PD-1 and PD-L1 protein in 758 stage I-IV NSCLCs from 3 independent cohorts represented in tissue microarray format. The targets were selectively measured in cytokeratin+ tumor epithelial cells, CD3+ T-cells, CD4+ T-helper cells, CD8+ cytotoxic T-cells, CD20+ B-lymphocytes and CD68+ tumor-associated macrophages. We determined the association between the targets, clinico-pathological/molecular variables and survival. Genomic analyses of lung cancer cases from TCGA was also performed. Results VISTA protein was detected in 99% of NSCLCs with a predominant membranous/cytoplasmic staining pattern. Expression in tumor and stromal cells was seen in 21% and 98% of cases, respectively. The levels of VISTA were positively associated with PD-L1, PD-1, CD8+ T-cells and CD68+ macrophages. VISTA expression was higher in T-lymphocytes than in macrophages; and in cytotoxic T-cells than in T-helper cells. Elevated VISTA was associated with absence of EGFR mutations and lower mutational burden in lung adenocarcinomas. Presence of VISTA in tumor compartment predicted longer 5-year survival. Conclusions VISTA is frequently expressed in human NSCLC and shows association with increased TILs, PD-1 axis markers, specific genomic alterations and outcome. These results support the immuno-modulatory role of VISTA in human NSCLC and suggests its potential as therapeutic target.

show abstract

Section: Discussionsupporting

confidence: 89%

Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non–Small Cell Lung Cancer

Villarroel‐Espíndola

Datar

et al. 2018

Clinical Cancer Research

172

150

View full text Add to dashboard Cite

show abstract

“…In this article, we revealed that the expression of LAIR‐1 was positively related to IDO. Several studies have established that immune checkpoints, such as PD‐1 (programmed death‐1), B7‐H3 (B7 homolog 3 protein), and VISTA (V‐domain Ig suppressor of T cell activation), are drivers of immune suppression in OSCC . We also observed a significant correlation with the expression of LAIR‐1 and B7‐H3 and VISTA.…”

Section: Discussionsupporting

confidence: 65%

“…Several studies have established that immune checkpoints, such as PD-1 (programmed death-1), B7-H3 (B7 homolog 3 protein), and VISTA (V-domain Ig suppressor of T cell activation), are drivers of immune suppression in OSCC. 5,15,36,37 We also observed a significant correlation with the expression of LAIR-1 and B7-H3 and VISTA. Taken together, we suspect that LAIR-1 is likely to exert immune suppressive function in OSCC and may serve as a therapeutic target in combination with other immune checkpoints.…”

Section: Discussionsupporting

confidence: 62%

See 1 more Smart Citation

LAIR‐1 overexpression and correlation with advanced pathological grade and immune suppressive status in oral squamous cell carcinoma

Yang

Zhang

et al. 2018

Head & Neck

Self Cite

View full text Add to dashboard Cite

Background This study aims to investigate the characteristic role of inhibitory receptor leukocyte‐associated immunoglobulin‐like receptor 1 (LAIR‐1) in oral squamous cell carcinoma (OSCC). Methods The expressions of LAIR‐1 and other immune‐related molecules were detected in a human OSCC tissue microarray. LAIR‐1 expression difference among different clinicopathological parameters was analyzed. The correlations of LAIR‐1 with several immune‐related markers were assessed. Results Compared with dysplasia and oral mucosa, the expression of LAIR‐1 was significantly upregulated in the stroma of OSCC, and its overexpression was correlated with advanced pathological grade. Overexpression of LAIR‐1 was significantly associated with tumor‐associated macrophage and myeloid‐derived suppressor cell markers (CD68, CD163; CD33, CD11b), indoleamine 2,3‐dioxygenase (IDO) and two immune checkpoints (B7‐H3 and VISTA). Conclusions Overexpression of LAIR‐1 was associated with advanced pathological grade and correlated with immune suppressive features in OSCC. Further studies are required to identify the specific immunological role of LAIR‐1.

show abstract

“…48,77,86) V domain-containing Ig suppressor of T-cell activation (VISTA)BothLeads to T-cell exhaustion and T-reg recruitment in the microenvironment (87,88). …”

mentioning

confidence: 99%

Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer

Kok

2020

Front. Oncol.

View full text Add to dashboard Cite

Starting in 2014, large phase III clinical trials began to disclose the study results of using programmed death (PD)-1 immune checkpoint inhibitors (ICIs) (pembrolizumab, nivolumab) and PD-ligand (L)1 (atezolizumab, durvalumab, avelumab) ICIs immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). In the recurrent and metastatic (R/M), cisplatin-refractory setting, nivolumab achieved a 2.2-fold increase of the median 1-year overall survival as compared with investigators' choice of salvage chemotherapy (36.0 vs. 16.6%). A paradigm shift to the winning regimen, pembrolizumab combined with platinum and infusional fluorouracil, has outperformed the past gold standard of cetuximab-based platinum and fluorouracil combination in terms of overall survival (median, 13.6 vs. 10.1 mo) when administered as the first-line treatment for R/M HNSCC. Nevertheless, many patients still did not respond to the PD-1/PD-L1 checkpoint inhibitor treatment, indicating innate, adapted, or quickly acquired resistance to the immunotherapy. The mechanisms of resistance to ICIs targeting the PD-1/PD-L1 signaling pathway in the context of HNSCC are the focus of this review. The past 5 years have seen improved understanding of the mechanisms underlying checkpoint inhibition resistance in tumor cells, such as: tumor cell adaption with malfunction of the antigen-presenting machinery via class I human leukocyte antigen (HLA), reintroduction of cyclin D-cyclin-dependent kinase (CDK) 4 complex to cell cycles, enrichment of CD44+ cancer stem-like cells, or development of inactivating mutation in IKZF1 gene; impairment of T-cell functions and proliferation through mutations in the interferon-γ-regulating genes, suppression of the stimulator of interferon genes (STING) pathway, or resulted from constitutional nutritional iron deficiency state; metabolic reprogramming by cancer cells with changes in metabolites such as GTP cyclohydrolase 1, tetrahydrobiopterin, kynurenine, indoleamine 2,3-dioxygenase, and arginase 1; defective dendritic cells, CD-69 sufficient state; and the upregulation or activation of the alternative immune checkpoints, including lymphocyte activation gene-3 (LAG3), T-cell Kok Immune Evasion From PD-1/PD-L1 Immunotherapy immunoglobulin and ITIM domain (TIGIT)/CD155 pathway, T-cell immunoglobulin mucin-3 (TIM-3), and V domain-containing Ig suppressor of T-cell activation (VISTA). Several potential biomarkers or biosignatures, which could predict the response or resistance to the PD-1/PD-L1 checkpoint immunotherapy, are also discussed.

show abstract

Expression of VISTA correlated with immunosuppression and synergized with CD8 to predict survival in human oral squamous cell carcinoma

Cited by 139 publications

References 39 publications

Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non–Small Cell Lung Cancer

Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non–Small Cell Lung Cancer

LAIR‐1 overexpression and correlation with advanced pathological grade and immune suppressive status in oral squamous cell carcinoma

Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer

Contact Info

Product

Resources

About