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Increased CD4 and CD8-positive T cell infiltrate signifies good prognosis in a subset of triple-negative breast cancer

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Abstract

Tumour-infiltrating lymphocytes (TILs) signify immune response to tumour in a variety of cancers including breast cancer. However, earlier studies examining the clinical significance of TILs in breast cancers have generated mixed results. There are only a few that address the relationship between TILs and clinical outcomes in triple-negative breast cancers (TNBC). The aim of this study is to evaluate the clinical significance of TILs that express CD4 + and CD8 + , in TNBC. Immunohistochemical staining of CD4 and CD8 was performed on tissue microarrays of 164 cases of TNBC. TILs were counted separately as intratumoral when within the cancer cell nests (iTILs) and as stromal when within cancer stroma (sTILs). High CD8 + iTILs and sTILs, and CD4 + iTILs correlated with histologic grade. On Kaplan–Meier analysis, a significantly better survival rate was observed in high CD8 + iTIL (disease-free survival, DFS: P = 0.004, overall survival, OS: P = 0.02) and both high CD4 + iTILs (DFS: P = 0.025, OS: P = 0.023) and sTILs (DFS: P = 0.01, OS: P = 0.002). In multivariate analysis, CD8 + iTILs (DFS: P = 0.0095), CD4 + sTILs (DFS: P = 0.0084; OS: P = 0.0118), and CD4 high CD8 high CD8 iTILs (DFS: P = 0.0121; OS: P = 0.0329) and sTILs (DFS: P = 0.0295) showed significantly better survival outcomes. These results suggest that high levels of both CD8 + iTILs and CD4 + sTILs as well as CD4 high CD8 high iTILs and sTILs are independent prognostic factors in TNBC.

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Acknowledgments

This study is a part of a research project approved by the SingHealth Centralised Institutional Review Board (CIRB Ref: 2013/664/F) and was funded by the Stratified Medicine Programme Office (Grant No: SMPO201302].

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Authors and Affiliations

  1. Department of Pathology, Ryukyu University Hospital, Okinawa, Japan

    Hirofumi Matsumoto

  2. Department of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Singapore, 169856, Singapore

    Aye Aye Thike, Joe Yeong, Puay Hoon Tan & Jabed Iqbal

  3. Division of Research, Singapore General Hospital, Singapore, Singapore

    Huihua Li

  4. Singapore Immunology Network, Agency of Science, Technology and Research, Singapore, Singapore

    Joe Yeong

  5. Department of Medical Oncology, National Cancer Centre, Singapore, Singapore

    Si-lin Koo & Rebecca Alexandra Dent

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  1. Hirofumi Matsumoto
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Correspondence to Jabed Iqbal.

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Matsumoto, H., Thike, A.A., Li, H. et al. Increased CD4 and CD8-positive T cell infiltrate signifies good prognosis in a subset of triple-negative breast cancer. Breast Cancer Res Treat 156, 237–247 (2016). https://doi.org/10.1007/s10549-016-3743-x

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  • DOI: https://doi.org/10.1007/s10549-016-3743-x

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