The expression of VISTA on CD4+ T cells associate with poor prognosis and immune status in non-small cell lung cancer patients.

Shengyao Ma,Weiyu Wang,Liya Qin,Yang Yang,Jinfeng Li,Xinling Wang,Meihua Qu,Hanyue Li,Huaijie Wang,Xiaoshan Cai

doi:10.17305/bjbms.2021.6531

Abstract

V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a novel negative immune checkpoint considered to be relevant to immunotherapy resistance and a potential target for immunotherapy. In this study, we investigated the relevance of VISTA expression on CD4+ T cells and clinical prognosis in non-small cell lung cancer (NSCLC) patients. Tumor tissue samples from 140 NSCLC patients were organized into a tissue microarray. The prognostic value of CD4+ VISTA+ T cells was analyzed through immunohistochemistry and multicolor fluorescence immunostaining. Fresh tumor tissue samples from 33 NSCLC patients were collected and similarly analyzed to confirm the immune state of patients with VISTA expression on CD4+ T cells by flow cytometry. CD4+ VISTA+ T cells were significantly more infiltrated in tumor tissues. The expression of VISTA on CD4+ T cells was correlated with the reduced overall survival of patients with NSCLC and presented a high rate of lymphocyte metastasis. The expression of VISTA on CD4+ T cells in tumor tissue showed low secretion of cytokines including IFN-γ, IL-2, IL-4, IL-10, IL-17, and IL-12p70. The expression of VISTA on CD4+ T cells could regulate tumor immunity and serve as a prognostic indicator for survival outcomes.

Highlights

In 2020, on an international scale, there was 2.2 million (11.4%) new cases of lung cancer and 1.8 million (18%) deaths [1]
CD4+ V-domain immunoglobulin suppressor of T-cell activation (VISTA)+ T cells expression is increased in tumor tissue compared with the corresponding peritumor tissue To verify the expression pattern of VISTA in fresh Non-small cell lung cancer (NSCLC) tumor tissues, we analyzed the expression of VISTA in freshly collected tissues and its paired peritumor tissues by flow cytometry
The results showed that CD4+ VISTA+ T cells were significantly increased in tumor tissues compared to peritumor tissues (Figure 2A-B), while no significant difference was seen with CD45+ VISTA+ cells and CD8+ VISTA+ T cells (Figure 2C-F)

Summary

Introduction

In 2020, on an international scale, there was 2.2 million (11.4%) new cases of lung cancer and 1.8 million (18%) deaths [1]. The interaction between tumor cells and tumor microenvironment (TME) serves a critical function in tumor occurrence, progression, metastasis, and drug resistance [3, 4]. Immune cells in TME could influence the growth and evolution of tumor cells, and the cross-talking of immune cells with tumor cells significantly affects the long-term outcomes in tumor patients [5, 6]. Immune checkpoints (ICs) have critical roles in modulating immune responses [7, 8]. These inhibitory ICs may be an effective tumor-targeting factor. The presentation of new ICs and their expression and function would possess value in cancer immunotherapy

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Results

Conclusion