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Expression of the immune checkpoint VISTA in breast cancer

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Abstract

V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint that is an emerging target for cancer immunotherapy. This study aimed to investigate the expression of VISTA and its association with clinicopathologic parameters as weNll as with the key immune markers including programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) in invasive ductal carcinoma (IDC) of the breast. Immunohistochemistry was used to detect VISTA, PD-1, PD-L1, and CD8 in tissue microarrays from 919 patients with IDC (N = 341 in the exploratory cohort and  = 578 in the validation cohort). VISTA was expressed on the immune cells of 29.1% (267/919) of the samples and on the tumor cells of 8.2% (75/919). VISTA was more frequently expressed in samples that were estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor 2-positive, poorly differentiated, human epidermal growth factor receptor 2-enriched, and consisting of basal-like tumors. VISTA on immune cells correlated with PD-1, PD-L1, stromal CD8, and tumor-infiltrating lymphocyte expression and was an independent prognostic factor for improved relapse-free and disease-specific survival in patients with estrogen receptor-negative, progesterone receptor-negative, and basal-like IDC. These findings support therapeutic strategies that modulate VISTA expression, perhaps in combination with PD-1/PD-L1 blockade, in human breast cancer immunotherapy.

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  • 18 June 2020

    The original version of this article unfortunately contained a mistake. The correct information is given below.

Abbreviations

AJCC:

American Joint Committee on Cancer

CTLA4:

Cytotoxic T-lymphocyte-associated protein 4

CK:

Cytokeratin

DSS:

Disease-specific survival

EGFR:

Epidermal growth factor receptor

ER:

Estrogen receptor

HER2:

Human epidermal growth factor receptor 2

IC:

Immune cell

IDC:

Invasive ductal carcinoma

LAG-3:

Lymphocyte activation gene 3

PR:

Progesterone receptor

REMARK:

Reporting Recommendations for Tumor Marker Prognostic Studies

RFS:

Relapse-free survival

TCGA:

The Cancer Genome Atlas

TC:

Tumor cell

TIM-3:

T-cell Immunoglobulin and mucin domain-containing molecule 3

TILs:

Tumor infiltrating lymphocytes

TMA:

Tumor tissue microarray

VISTA:

V-domain Ig suppressor of T-cell activation

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Funding

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81971475 and 81672648) and the Chinese Academy of Medical Sciences Initiative for Innovative Medicine (Nos. CAMS-2017-I2M-1–002 and CAMS-2016-I2M-1–001). The funders of the study had no role in the design of the study, the collection, analysis, and interpretation of data, or in writing the manuscript.

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Contributions

YX and JC made substantial contributions to the conception, design, and critical revision of the manuscript. LZ, SY, and SM made substantial contributions to tissue microarray construction, acquisition, and interpretation of the data, and drafting of the manuscript. YZ and MZ made substantial contributions to immunohistochemistry experiments and the interpretation of data. All authors read and approved the final manuscript.

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Correspondence to Jie Chen or Yang Xiang.

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The authors declare that they have no conflicts of interest.

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The study was approved by the Institutional Review Board of Peking Union Medical College Hospital (approval number S-K995).

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Zong, L., Mo, S., Yu, S. et al. Expression of the immune checkpoint VISTA in breast cancer. Cancer Immunol Immunother 69, 1437–1446 (2020). https://doi.org/10.1007/s00262-020-02554-3

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