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
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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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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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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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DOI: https://doi.org/10.1007/s00262-020-02554-3