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Prognostic value of tumor infiltrating lymphocyte subsets in breast cancer depends on hormone receptor status

  • Preclinical Study
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Abstract

Purpose

Interaction between immune-regulatory proteins and tumor infiltrating lymphocytes (TILs) is complex, and their associations may have significant clinical implications. This study was designed to evaluate the relationships between immunomodulatory proteins and TIL subsets and their impact on prognosis in breast cancer.

Methods

377 invasive breast cancer cases were selected, and immunohistochemistry was performed for HLA-A, HLA-ABC, and indoleamine 2,3-dioxygenase (IDO); CD4+, CD8+, and FOXP3+ T cells were counted in intratumoral and stromal areas for both absolute numbers as well as their ratios.

Results

While HLA-ABC and HLA-A expressions showed a positive correlation with CD8+ and FOXP3+ TIL infiltration, IDO expression showed a negative correlation with FOXP3+/CD4+ and FOXP3+/CD8+ T cell ratios. Expressions of HLA-ABC, HLA-A, and IDO shared an association with negative estrogen receptor status. Infiltration of CD4+, CD8+, and FOXP3+ TILs was significantly higher in tumors with high histologic grade, negative hormone receptor status, HER2 amplification, high Ki-67 index, and p53 overexpression. In survival analyses, increased CD4+ TIL infiltration was associated with better prognosis of the patients while other TIL subset infiltration and expression of immunomodulatory proteins had no prognostic significance. In subgroup analyses, high CD4+ TIL infiltration was revealed as an independent good prognostic factor in hormone receptor-negative subgroup while high FOXP3+/CD8+ T cell ratio was found to be an independent adverse prognostic factor in hormone receptor-positive subgroup, especially in luminal A subtype.

Conclusion

CD4+ TIL subset and FOXP3+/CD8+ T cell ratio have different prognostic significance in breast cancer according to hormone receptor status.

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Funding

This study was funded by a Grant from the National Research Foundation of Korea (NRF)’s Basic Science Research Program funded by the Ministry of Science, ICT, and Future Planning (Grant No. NRF-2015R1A2A2A01007907) to Park SY.

Author information

Authors and Affiliations

  1. Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea

    Yul Ri Chung & So Yeon Park

  2. Department of Pathology, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Songnam, Gyeonggi, 13620, Republic of Korea

    Hyun Jeong Kim & So Yeon Park

  3. Department of Pathology, Yeungnam University Medical Center, Daegu, Republic of Korea

    Min Hye Jang

Authors
  1. Yul Ri Chung
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  2. Hyun Jeong Kim
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Correspondence to So Yeon Park.

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Conflict of interest

Chung YR declares that she has no conflict of interest. Kim HJ declares that she has no conflict of interest. Jang MH declares that she has no conflict of interest. Park SY declares that she has no conflict of interest.

Ethical approval

This study was approved by the institutional review board (protocol # B-1601/332-304). 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.

Informed consent

Institutional review board waived the requirement for obtaining informed consent for this study.

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Chung, Y.R., Kim, H.J., Jang, M.H. et al. Prognostic value of tumor infiltrating lymphocyte subsets in breast cancer depends on hormone receptor status. Breast Cancer Res Treat 161, 409–420 (2017). https://doi.org/10.1007/s10549-016-4072-9

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  • DOI: https://doi.org/10.1007/s10549-016-4072-9

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