Intestinal microbiota modulates tumour response in cancer patients

Over the last 10 years, tremendous advances have been made for cancer patients using new treatment strategies, including immune checkpoint inhibitors that target cytotoxic T-lymphocyte-associated antigen (CTLA-4) and programmed death 1 (PD-1) protein. However, therapeutic responses to these new treatment modalities are often heterogeneous, and some non-responder patients have been reported. The intestinal microbiome has been suggested to be an important host factor for non-responder patients, along with tumour genomics. Previous studies on microbiota and cancer have mainly focused on alterations in the intestinal microbiota of cancer patients (oncobiome) or microbiota precursors in order to define early-stage cancers, mainly colorectal cancers. However, promising new results regarding the influence of intestinal microbiota on anti-tumour immune responses have emerged. Two new studies were published in the first issue of Science this year.

• Gopalakrishnan et al. [2] evaluated the intestinal and oral microbiome in 112 patients with malignant melanoma, receiving anti-PD-1 immunotherapy, and compared baseline microbiota composition between cancer responders and non-responders. They revealed significant differences in the diversity and composition of intestinal microbiota between responders and non-responders. Significantly higher alpha diversity and relative abundance of Ruminococcaceae/Faecalibacterium was observed in responders, and this favourable intestinal microbiota composition has been suggested to enhance systemic and anti-tumour immunity among patients with melanoma. Patients with a low diversity and relatively high abundance of Bacteroidales (unfavourable intestinal microbiome) have impaired anti-tumour immune responses.

• Matson et al. [3] also evaluated the composition of baseline intestinal microbiota in patients with metastatic melanoma before receiving anti-PD-L1 therapy. Among the responders to treatment, Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium have been shown to be predominant members of the microbiota. These authors suggest that the commensal microbiome may exhibit a mechanistic impact on anti-tumour immunity in patients with metastatic melanoma. In the light of the results from these two previous clinical studies, it is thought that baseline intestinal microbiota may play a critical role in mediating the immune- stimulant response in melanoma patients receiving immunotherapy, such as anti-PD-L1 therapy. Further prospective studies are needed to reveal the precise interactions between the microbiome and cancer, not only in melanoma patients, but in terms of potential relevance for all types of cancer and the different treatment strategies.