T-cell modulation by cyclophosphamide for tumour therapy

Immunology. 2018 May;154(1):62-68. doi: 10.1111/imm.12913. Epub 2018 Mar 9.

Abstract

The power of T cells for cancer treatment has been demonstrated by the success of co-inhibitory receptor blockade and adoptive T-cell immunotherapies. These treatments are highly successful for certain cancers, but are often personalized, expensive and associated with harmful side effects. Other T-cell-modulating drugs may provide additional means of improving immune responses to tumours without these disadvantages. Conventional chemotherapeutic drugs are traditionally used to target cancers directly; however, it is clear that some also have significant immune-modulating effects that can be harnessed to target tumours. Cyclophosphamide is one such drug; used at lower doses than in mainstream chemotherapy, it can perturb immune homeostasis, tipping the balance towards generation of anti-tumour T-cell responses and control of cancer growth. This review discusses its growing reputation as an immune-modulator whose multiple effects synergize with the microbiota to tip the balance towards tumour immunity offering widespread benefits as a safe, and relatively inexpensive component of cancer immunotherapy.

Keywords: T cells; cancer; cyclophosphamide; regulatory T cells.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cyclophosphamide / therapeutic use*
  • Humans
  • Immunologic Factors / therapeutic use*
  • Immunotherapy / methods*
  • Lymphocytes, Tumor-Infiltrating / drug effects*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Tumor Escape / drug effects

Substances

  • Antineoplastic Agents
  • Immunologic Factors
  • Cyclophosphamide