Sunday, February 14, 2016

Intestinal bacteria as a way to determine risk for ipi induced colitis!

I've previously talked about how certain cooties in our gut can serve us well in all sorts of ways.  There was even a study noted in this link: Cooties in our gut keep us skinny, smart, and cure cancer? that found Bifidobacterium could promote antitumor immunity and facilitate anti-PD-L1 efficacy!  Now there is this: 

Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis.  Dubin, Callahan, Ren, Wolchok, et al.  Nat Commun. 2016 Feb 2.

The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota's composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy.

It would certainly be helpful to have a head's up about who is more at risk for the development of colitis when treated with immunotherapy!  Perhaps other options would serve the patient better or if immunotherapy is undertaken anyway, a prior warning could promote a more watchful eye and aggressive, prompt treatment should any adverse symptoms appear.  Best - c

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