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Review
. 2019 Feb;20(2):e77-e91.
doi: 10.1016/S1470-2045(18)30952-5.

Modulating the microbiome to improve therapeutic response in cancer

Jennifer L McQuade  1 , Carrie R Daniel  2 , Beth A Helmink  3 , Jennifer A Wargo  4
Affiliations
Review

Modulating the microbiome to improve therapeutic response in cancer

Jennifer L McQuade et al. Lancet Oncol. 2019 Feb.

Abstract

Although novel therapies, including immunotherapy, have dramatically improved outcomes for many patients with cancer, overall outcomes are heterogeneous and existing biomarkers do not reliably predict response. To date, predictors of response to cancer therapy have largely focused on tumour-intrinsic features; however, there is growing evidence that other host factors (eg, host genomics and the microbiome) can substantially affect therapeutic response. The microbiome, which refers to microbiota within a host and their collective genomes, is becoming increasingly recognised for its influence on host immunity, as well as therapeutic responses to cancer treatment. Importantly, microbiota can be modified via several different strategies, affording new angles in cancer treatment to improve outcomes. In this Review, we examine the evidence on the role of the microbiome in cancer and therapeutic response, factors that influence and shape host microbiota, strategies to modulate the microbiome, and present key unanswered questions to be addressed in ongoing and future research.

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Conflict of interest statement

Declaration of interests

JAW is an inventor on a US patent application (PCT/US17/53.717) submitted by the University of Texas MD Anderson Cancer Center that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. JAW is also a paid speaker for Imedex, Dava Oncology, Omniprex, Illumina, Gilead, MedImmune, and Bristol-Myers Squibb, a consultant and advisory board member for Roche-Genentech, Novartis, Astra-Zeneca, GlaxoSmithKline, Bristol-Myers Squibb, Merck, and Microbiome DX, reports clinical trial support from GlaxoSmithKline, Roche/Genentech, Bristol-Myers Squibb, and Novartis, and is a clinical and scientific advisor at Microbiome DX and a consultant at Biothera Pharma, Merck Sharp and Dohme.

All other authors declared no conflicts of interest.

Figures

Figure 1:
Figure 1:. Complex interplay of the gut and tumour microbiome and the host immune system
APCs=antigen-presenting cells. IgA=immunoglobulin A. MHC=major histocompatibility complex. Tregs=regulatory T cells. MDSCs=myeloid-derived suppressor cells. PD-L1=programmed death ligand 1.
Figure 2:
Figure 2:. Factors affecting the gut microbiome
HLA= human leukocyte antigen.
Figure 3:
Figure 3:. Questions to consider in clinical trial design for microbiome modulation in cancer
FMT=faecal microbiota transplant. ctDNA=circulating tumour DNA. RECIST=Response Evaluation Criteria in Solid Tumors. irRC= immune-related response criteria. PD-1=programmed death receptor-1.
See this image and copyright information in PMC

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