ELCC 2019 - Is there a role for gut microbiome in clinical responses to lung cancer immunotherapy?


  • Michael Simm
  • Oncology Conference reports
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Takeaway

The microbiome of the gut may influence the interactions between cancer therapies and the immune system. This could potentially be exploited for beneficial manipulations of that balance through the administration of probiotics, prebiotics, or via fecal microbiome transfer.

Why this matters

Microbes of the gut may metabolize cancer drugs and affect processes such as inflammation, immune stimulation, and cytoprotection. A better understanding of these processes may open new therapeutic strategies.

Study design

Review of recent data from animal models and human patients.

Key results

  • Administration of antibiotics was associated with reduced progression free survival (PFS) of 3.5 months versus 5.2 months and overall survival (OS) to 12.1 months from 20.8 months in one study of 175 advanced cancer patients treated with PD-1/PD-L1 inhibitors.
  • Dysbiosis after concomitant antibiotic administration seems to influence resistance to immune checkpoint inhibition with PD-1 blockade in cancer patients and mice with established tumors.
  • The species most associated with responses in NSCLC and renal cell carcinoma was Akkermansia muciniphila. It was overrepresented at the time of diagnosis in the stool samples of those cancer patients that benefitted from PD-1 checkpoint inhibition therapy. Another “suspect” was Enterococcus hirae.
  • In mice, fecal microbiota transplantation from responding cancer patients stool conferred sensitivity to PD-1 blockade.

Limitations

A large part of research was done in mouse models. No prospective interventional studies that could separate correlations from causation.

Funding

European Commission and other public funds.