Association Between Gut Microbiome and Responses to Anti-PD-1 Therapy in Patients with Metastatic Melanoma

Gut microbiome may influence the response to checkpoint blockade

Research findings presented at 2017 ASCO-SITC Clinical Immuno-Oncology Symposium (23-25 February 2017, Orlando, US) underline differences in the diversity and composition of the gut microbiome in responders vs non-responders to anti-PD1 therapy for metastatic melanoma. The results have far-reaching implications and suggest that modifications to the gut microbiome could potentially enhance therapeutic responses to immune checkpoint blockade.

In the study background, the authors explained that there is a growing appreciation of the role of the microbiome in cancer-related outcomes. Recent evidence in murine models suggests that modulation of the gut microbiome may enhance responses to immune checkpoint blockade in melanoma. However, it was not until now investigated in patients.

The study team collected 222 oral and 113 gut microbiome samples from 228 patients with metastatic melanoma, from whom 110 patients have been treated with anti-PD1 therapy. Patients were classified as either responders or non-responders based on RECIST criteria.

In order to characterize the diversity and composition of the microbiomes, 16S rRNA gene sequencing was performed. Immune profiling by using 7-marker immunohistochemistry panel was performed in available tumours at baseline.

The study team observed significant differences in the diversity and composition of the gut microbiome in responders vs non-responders to PD1 blockade at baseline, but no clear differences in oral microbiomes. Specifically, responders had a significantly higher alpha diversity compared to non-responders (p = 0.017). Notable differences were also seen in the composition of the gut microbiome of responders vs non-responders.

Immune profiling demonstrated significantly increased immune infiltrates in baseline tumour samples of responders, with a positive correlation between CD8, CD3, PD1 and FoxP3 T-cell density and abundance of specific bacteria enriched in responders (e.g. Faecalibacterium).

In their work, the authors demonstrated that differential bacterial “signatures” exist in the gut microbiome of responders and non-responders to anti-PD1 therapy for metastatic melanoma and these insights could be used to derive in the future actionable strategies to enhance responses.

Lead study investigator who presented the study results is Vancheswaran Gopalakrishnan, MPH, a PhD candidate at The University of Texas MD Anderson Cancer Center. The results were discussed by Shridar Ganesan, MD, PhD, of the Rutgers Cancer Institute of New Jersey who said that the response to immunotherapy depends not only on tumour characteristics but also on the immune microenvironment, which can certainly be influenced by host factors.

Reference

Gopalakrishnan V, Spencer C, Reuben A, et al. Association of diversity and composition of the gut microbiome with differential responses to PD-1 based therapy in patients with metastatic melanoma.J Clin Oncol 35, 2017 (suppl 7S; abstract 2)