Immunostimulatory Properties of Chemotherapy in Breast Cancer: From Immunogenic Modulation Mechanisms to Clinical Practice

Front Immunol. 2022 Jan 5:12:819405. doi: 10.3389/fimmu.2021.819405. eCollection 2021.

Abstract

Breast cancer (BC) is the most common malignancy among females. Chemotherapy drugs remain the cornerstone of treatment of BC and undergo significant shifts over the past 100 years. The advent of immunotherapy presents promising opportunities and constitutes a significant complementary to existing therapeutic strategies for BC. Chemotherapy as a cytotoxic treatment that targets proliferation malignant cells has recently been shown as an effective immune-stimulus in multiple ways. Chemotherapeutic drugs can cause the release of damage-associated molecular patterns (DAMPs) from dying tumor cells, which result in long-lasting antitumor immunity by the key process of immunogenic cell death (ICD). Furthermore, Off-target effects of chemotherapy on immune cell subsets mainly involve activation of immune effector cells including natural killer (NK) cells, dendritic cells (DCs), and cytotoxic T cells, and depletion of immunosuppressive cells including Treg cells, M2 macrophages and myeloid-derived suppressor cells (MDSCs). Current mini-review summarized recent large clinical trials regarding the combination of chemotherapy and immunotherapy in BC and addressed the molecular mechanisms of immunostimulatory properties of chemotherapy in BC. The purpose of our work was to explore the immune-stimulating effects of chemotherapy at the molecular level based on the evidence from clinical trials, which might be a rationale for combinations of chemotherapy and immunotherapy in BC.

Keywords: breast cancer; chemotherapy; clinic trial; immunogenic modulation; immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity / drug effects
  • Alarmins / genetics
  • Alarmins / metabolism
  • Animals
  • Antigens, Neoplasm / immunology
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology*
  • Clinical Trials as Topic
  • Disease Management
  • Disease Susceptibility
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Immune Checkpoint Proteins / genetics
  • Immune Checkpoint Proteins / metabolism
  • Immunity / immunology*
  • Immunity, Innate / drug effects
  • Immunomodulation / drug effects*
  • Treatment Outcome

Substances

  • Alarmins
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Immune Checkpoint Proteins