Checkpoint Inhibitors and Their Application in Breast Cancer

Davide Bedognetti, Cristina Maccalli, Salha B.J. Al Bader, Francesco M. Marincola, Barbara Seliger

Research output: Contribution to journalReview article

28 Citations (Scopus)

Abstract

Immune checkpoints are crucial for the maintenance of self-tolerance and for the modulation of immune responses in order to minimize tissue damage. Tumor cells take advantage of these mechanisms to evade immune recognition. A significant proportion of tumors, including breast cancers, can express co-inhibitory molecules that are important formediating the escape from T cell-mediated immune surveillance. The interaction of inhibitory receptors with their ligands can be blocked by specific molecules. Monoclonal antibodies (mAbs) directed against the cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and, more recently, against the programmed cell death protein 1 (PD1), have been approved for the therapy of melanoma (anti-CTLA4 and anti-PD1 mAbs) and non-small cell lung cancer (anti-PD1 mAbs). Moreover, inhibition of PD1 signaling has shown extremely promising signs of activity in breast cancer. An increasing number of molecules directed against other immune checkpoints are currently under clinical development. In this review, we summarize the evidence supporting the implementation of checkpoint inhibition in breast cancer by reviewing in detail data on PD-L1 expression and its regulation. In addition, opportunities to boost anti-tumor immunity in breast cancer with checkpoint inhibitor-based immunotherapies alone and in combination with other treatment options will be discussed.

Original languageEnglish
Pages (from-to)108-115
Number of pages8
JournalBreast Care
Volume11
Issue number2
DOIs
Publication statusPublished - 1 Apr 2016

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Keywords

  • Antibody therapy
  • Biomarker
  • Biomarker
  • Breast cancer
  • Breast cancer
  • Immune system
  • Immune system
  • Immunomodulation
  • Immunomodulation
  • Immunotherapy
  • Immunotherapy
  • Tumor marker
  • Tumor markerAntibody therapy

ASJC Scopus subject areas

  • Surgery
  • Oncology

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