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Prognostic and therapeutic role of tumor-infiltrating lymphocyte subtypes in breast cancer

Abstract

Increased levels of total tumor-infiltrating lymphocytes (TILs) are generally associated with good prognosis in several breast cancer subtypes. Subtypes of TILs impact both tumor cells and immune cells in a variety of different ways, leading to either a pro-tumor or antitumor effect. Tumor-infiltrating CD8+ T cells and natural killer (NK) cells perform as effector cells against tumor cells and are associated with better clinical outcome. Immunotherapy approaches that improve the antitumor activity and proliferation of CD8+ T and NK cells include PD-1/PD-L1 blockade, CAR T cell therapy, or ex vivo-stimulated NK cells. A subset of CD8+ T cells, tissue-resident memory T cells, has also recently been associated with good prognosis in breast cancer patients, and has potential to serve as a predictive biomarker and therapeutic target. Tumor-infiltrating B cells also secrete apoptosis-inducing IgG antibodies and can act as antigen-presenting cells to prime CD4+ and CD8+ T cells. On the other hand, regulatory T and regulatory B cells modulate the immune response from CD8+ T cells and NK cells by secreting immunosuppressive cytokines and inhibiting maturation of antigen-presenting cells (APCs). These regulatory cells are typically associated with poor prognosis, therefore rendering suppression of their regulatory function a key immunotherapeutic strategy.

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Funding

This work was supported by the National Cancer Institute of the National Institutes of Health under Award Number R44CA217534, the Wayne D. Kuni & Joan E. Kuni Foundation, and OHSU Center for Women’s Health Circle of Giving Award. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH and US government.

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Conceptualization, M.N. and W.N., literature search, M.N., writing—original draft preparation, M.N.; writing—review and editing, M.N., W.N., S.L., W.Y.; funding acquisition, W.Y., W.N. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Wassana Yantasee.

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Nelson, M.A., Ngamcherdtrakul, W., Luoh, SW. et al. Prognostic and therapeutic role of tumor-infiltrating lymphocyte subtypes in breast cancer. Cancer Metastasis Rev 40, 519–536 (2021). https://doi.org/10.1007/s10555-021-09968-0

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Keywords

  • Breast cancer
  • Immunotherapy
  • Tumor microenvironment
  • TILs
  • T cells