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

• Published in: Breast cancer (Tokyo, Japan) Vol. 24; no. 1; pp. 3 - 15
• Main Authors: Burugu, Samantha, Asleh-Aburaya, Karama, Nielsen, Torsten O.
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.01.2017; Springer
• Subjects: B cells; Biomarkers, Tumor - immunology; Breast cancer; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Cancer; Cancer Research; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; CTLA-4 Antigen - immunology; Development and progression; Diagnosis; Female; Humans; Immune response; Immunity, Innate; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Macrophages - immunology; Macrophages - pathology; Medicine; Medicine & Public Health; Oncology; Oncology, Experimental; Prognosis; Programmed Cell Death 1 Receptor; Special Feature; Surgery; Surgical Oncology; T cells; T-Lymphocytes, Regulatory - immunology; Tumor Microenvironment - immunology; Immune microenvironment; Breast cancer; Prognosis; Tumor-infiltrating lymphocytes; Prediction
• ISSN: 1340-6868; 1880-4233
• DOI: 10.1007/s12282-016-0698-z

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.