T-cell modulation by cyclophosphamide for tumour therapy

Ellyn Hughes, Martin Scurr, Emma Campbell, Emma Jones, Andrew Godkin, Awen Gallimore, Ellyn Hughes, Martin Scurr, Emma Campbell, Emma Jones, Andrew Godkin, Awen Gallimore

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.

© 2018 The Authors. Immunology Published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Proposal for measuring the immune‐modulating effects of cyclophosphamide (CY). Future studies of the effects of CY should incorporate baseline measurements and aim to perform analyses of immune cell subsets at many time‐points post‐administration. Such analyses should take into account numbers, proportions and function of immune cell subsets as well as cancer‐specific T‐cell responses. Measuring the impact on intestinal permeability and microbial translocation should also be considered. p.o. per oral, i.v. intravenous.

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