Monday, November 9, 2015

Gut microbes fuel effectiveness of anti-CTLA-4 cancer immunotherapy. Part I

Recently two back-to-back papers in Science Express received much media attention. These studies claim that gut microbial flora influence clinical effectiveness of checkpoint inhibitors approved for cancer immunotherapy. I am going to review and provide my analysis of these studies.

First paper I will review came from European team led by Laurence Zitvogel. Of note, her team had another tumor immunology paper just 1 week ago in Science. First notable thing about her publications is the number of names included as authors. Her lab had done this since I first heard about her studies in 2007. Either she is a good collaborator or everyone in her lab is get credit for everyone else's work as a matter of right [definitely good for career].

For example, they showed that inhibition of cancer growth by anti-CTLA-4 antibody injected in germ-free or antibiotic-treated mice was not as good as in control WT mice

Analysis of gut flora revealed that presence of specific set of microbes [B. fragilis, for example] were required to show anti-cancer effectiveness of anti-CTLA-4 antibody.

Now these result are quite preliminary and it is not clear how microbes are enhancing anti-CTLA-4 effectiveness. For example, some microbes can live within growing tumor tissue and anti-CTLA-4 therapy simply unleashes immune response against them destroying tumor tissue in the process. There is a possibility that microbes support presence of cross-reactive T cells required to target tumor antigens when they are unleashed by anti-CTLA-4 immunotherapy. In all, based on this paper we can't say how microbes help anti-CTLA-4 and how much this "help" is meaningful in clinical settings. Maybe second paper will provide some ideas in this regard. Stay tuned for next review. 

David Usharauli   

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