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Co-expression of HLA-I loci improved prognostication in HER2+ breast cancers

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Abstract

The underlying basis for cancer immune evasion is important for effective immunotherapy and prognosis in breast cancers. Human leucocyte antigens (HLA)-I comprising three classical antigens (HLA-A, -B and -C) is mandatory for anti-tumor immunity. Its loss occurred frequently in many cancers resulting in effective immune evasion. Most studies examined HLA-I as a whole. Alterations in specific locus could have different clinical ramifications. Hence, we evaluated the expression of the three HLA-I loci in a large cohort of breast cancers. Low expression of HLA-A, -B and -C were found in 71.1%, 66.3%, and 60.2% of the cases. Low and high expression in all loci was found in 48.3% and 17.9% of the cases respectively. The remaining showed high expression in one or two loci. Cases with all HLA high expression (all HLA high) was frequent in the ER-HER2- (27.4%) and ER-HER2+ (23.1%) cases and was associated with characteristic pathologic features related to these tumor (higher grade, necrosis, high tumor infiltrating lymphocyte (TIL), pT stage, low hormonal receptor, high basal marker expression) (p ≤ 0.019). Interestingly, in HER2+ cancers, only cases with all HLA high and high TIL showed significantly better survival. In node positive cancers, concordant high HLA expression in primary tumors and nodal metastases was favorable prognostically (DFS: HR = 0.741, p < 0.001; BCSS: HR = 0.699, p = 0.003). The data suggested an important clinical value of a combined analysis on the co-expression HLA-I status in both primary and metastatic tumors. This could be a potential additional key component to be incorporated into TIL evaluation for improved prognostication.

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Acknowledgements

We thanked the Core Utilities for Cancer Genomics and Pathobiology, Anatomical and Cellular Pathology, The Chinese University of Hong Kong for their excellent technical support.

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Authors and Affiliations

  1. Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong

    Julia Y. Tsang, Chun-Sing Ho, Yun-Bi Ni, Yan Shao, Ivan K. Poon & Gary M. Tse

  2. Department of Pathology, Kwong Wah Hospital, Yau Ma Tei, Hong Kong

    Siu-Ki Chan

  3. Department of Pathology, Tuen Mun Hospital, Tuen Mun, Hong Kong

    Chun-Sing Ho, Sai-Yin Cheung & Ka-Ho Shea

  4. Department of Pathology, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines

    Monalyn Marabi

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Contributions

JT analyzed the data and wrote the paper; CH, YS, IP, MM performed the experiments; S-KC, S-YC, KS collected and arranged clinicopathological data of cases; GT conceived the idea for the paper, provided guidance and critically revised the paper. All authors read and approved the final version to be published.

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Correspondence to Gary M. Tse.

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Human and animal right statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by Joint Chinese University of Hong Kong- New Territories East Cluster clinical research ethics committee (Re: 2014.500).

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Tsang, J.Y., Ho, CS., Ni, YB. et al. Co-expression of HLA-I loci improved prognostication in HER2+ breast cancers. Cancer Immunol Immunother 69, 799–811 (2020). https://doi.org/10.1007/s00262-020-02512-z

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