Immune infiltrates in the breast cancer microenvironment: detection, characterization and clinical implication

Breast Cancer. 2017 Jan;24(1):3-15. doi: 10.1007/s12282-016-0698-z. Epub 2016 May 2.

Abstract

Although unlike melanoma, breast cancer is not generally viewed as a highly immunogenic cancer, recent studies have described a rich tumor immune microenvironment in a subset of breast cancers. These immune infiltrates, comprised cells from the innate and adaptive immune response, can be detected and characterized in biopsy specimens and have prognostic value. Tumor-infiltrating lymphocytes (TILs) represent the majority of mononuclear immune infiltrates in the breast tumor microenvironment and can be easily identified in formalin-fixed paraffin-embedded tissues after standard hematoxylin and eosin staining. High levels of TILs are most common in HER2+ and basal-like subtypes where they are associated with good prognosis and with response to certain therapies such as the anti-HER2 antibody trastuzumab. International collaborative efforts are underway to standardize the assessment of TILs so as to facilitate their implementation as a breast cancer biomarker. Using immunohistochemistry to further characterize TILs, recent reports describe the presence of important lymphocyte populations including CD8+ cytotoxic, FOXP3+ regulatory, and CD4+ helper and follicular T cells which have overlapping associations with prognosis and response to therapies. Moreover, recently identified immune checkpoint markers (PD-1, PD-L1) are present in some breast cancers, implying some cases might be especially amenable to immune checkpoint inhibitor treatment strategies which are being evaluated in a number of active clinical trials.

Keywords: Breast cancer; Immune microenvironment; Prediction; Prognosis; Tumor-infiltrating lymphocytes.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / immunology
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CTLA-4 Antigen / immunology
  • Female
  • Humans
  • Immunity, Innate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Macrophages / immunology
  • Macrophages / pathology
  • Programmed Cell Death 1 Receptor
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Microenvironment / immunology*

Substances

  • Biomarkers, Tumor
  • CTLA-4 Antigen
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor