Saturday, January 6, 2018

Microbiota-wide association studies and PD-1 immunotherapy

This week Science published 3 back-to-back studies with the findings that responses to PD-1 immunotherapy in cancer patients could be stratified based on presence of certain microbiota species (at least two of these studies were published couple of weeks back as first release papers). 

The trouble is that all three papers found different set of microbiota who they thought mediated responsiveness to PD-1 immunotherapy (dominated by Bifdobacterium, Akkermansiaor Faecalibacterium). 

In one study, it was actually a difference between set of beneficial microbiota versus nonbeneficial ones (not simply a single species), above certain ratio (>1.5), that determined responsiveness to PD-1 therapy.

Moreover, study of germ-free mice transplanted with opposite sets of microbiota (derived from 3 responders/nonresponders) were inconclusive because 1 set of microbiota from each group showed reverse effect with PD-1 immunotherapy. 

In summary, we have no clear understanding of these results. There is no way to predict if the same microbiota set would provide any benefit to a given patient. In general, presently microbiota research lacks direction and rules necessary to untangle its complexity

As far as I know, the model we have developed, SPIRAL, is the only one that provides a rational how to identify specific microbiota species. Right now it is just a guideline but when fully developed it will look similar to period table-like map that will make it easy to accurately pinpoint microbiota species relevant for antigen-specific immune response in any given individual.

posted by David Usharauli


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