Anthony L. Komaroff, MD reviewing Vétizou M et al. Science 2015 Nov 27. Sivan A et al. Science 2015 Nov 27. Snyder A et al. Science 2015 Nov 27.

In the past 5 years, several novel immunotherapies for cancer have emerged (NEJM JW Gen Med Jun 16 2015; [e-pub] and Science 2015; 348:62). One of the most exciting is “checkpoint inhibitors.” When malignant cells elicit a T-cell response, the activated T cells paradoxically produce “checkpoint” molecules (including CTLA-4 and PD-1) that abort the T-cell attack. However, monoclonal antibodies that inhibit these checkpoint molecules can unleash the T-cell attack on the tumor. Dramatic responses have been reported in some patients, but, in other patients, the therapies don’t work.

Using a mouse model of melanoma, two teams have found that particular gut bacteria might play a key role in determining the efficacy of checkpoint-inhibitor drugs. A U.S. team found that oral administration of Bifidobacterium, alone, improved tumor control; a PD-1 inhibitor, alone, had about the same effect. However, when the two agents were combined, tumor growth was abolished. The gut bacteria enhanced tumor-specific CD8+ T-cell function.

Using the same model, a French team found that the efficacy of anti–CTLA-4 therapy was eradicated by broad-spectrum antibiotics. Feeding the antibiotic-treated mice Bacteroidales species restored anti–CTLA-4 activity. This group also showed that anti–CTLA-4 therapy leads to a decrease in Bacteroidales species, thereby negatively affecting this therapy’s efficacy over time.

Comment

These two studies reveal yet another role for the gut microbiome in human health: the ability to influence immune responses to cancer. Although much more testing needs to be done, probiotics might someday be adjunctive therapy in treating human cancer.

CITATION(S):

  1.  Vétizou M et al. Anticancer immunotherapy by CTLA­4 blockade relies on the gut microbiota. Science 2015 Nov 27; 350:1079. (http://dx.doi.org/10.1126/science.aad1329) Abstract/FREE Full Text
  2. Sivan A et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD­L1 efficacy. Science 2015 Nov 27; 350:1084. (http://dx.doi.org/10.1126/science.aac4255) Abstract/FREE Full Text
  3. Snyder A et al. Could microbial therapy boost cancer immunotherapy? Science 2015 Nov 27; 350:1031.
    (http://dx.doi.org/10.1126/science.aad7706) Abstract/FREE Full Text