CTLA-4 Expression and Its Clinical Significance in Breast Cancer

Arch Immunol Ther Exp (Warsz). 2021 Jun 20;69(1):16. doi: 10.1007/s00005-021-00618-5.

Abstract

Breast cancer is the leading cause of women's death among all cancers. The main reason associated with this is the development of metastasis and therapy-resistant breast carcinoma (BC), which pose the main challenge of oncology nowadays. Evidence suggest that these tumors seem to have inhibitory mechanisms that may favor their progression and surveillance. Cancer cells can evade antitumor T cell responses by expressing some immune inhibitory molecules such as the cytotoxic T-lymphocyte antigen-4 (CTLA-4), whose clinical meaning has emerged in the last few years and is poorly understood in the BC context. This systematic literature review aims at identifying studies on CTLA-4 expression in BC, and address what is known about its clinical meaning. A literature search was performed in PubMed and LILACS databases, using the MESH terms "breast cancer"; "CTLA-4 Antigen/antagonists and inhibitors"; and "Lymphocytes, Tumor-Infiltrating/immunology", published in the last 10 years. In total, 12 studies were included in this review. Systematic review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Despite the small number of eligible studies, the literature reports some associations between CTLA-4 expression in the tumor microenvironment and worse BC outcomes, regardless of its molecular subtype. CTLA-4 expression in BC is a putative marker of clinical significance and a rationale therapeutic target in the emerging field of immunotherapy.

Keywords: Breast neoplasms; CTLA-4 antigen/antagonists and inhibitors; Flow cytometry; Immunohistochemistry; Ipilimumab; Lymphocytes; Tumor-infiltrating/immunology.

Publication types

  • Systematic Review

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / mortality
  • CTLA-4 Antigen / analysis
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / metabolism*
  • Cell Line, Tumor
  • Clinical Decision-Making
  • Disease-Free Survival
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology*
  • Immune Checkpoint Inhibitors / therapeutic use
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / prevention & control
  • Prognosis
  • Tumor Escape / drug effects
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology*

Substances

  • Biomarkers, Tumor
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immune Checkpoint Inhibitors