The EACR’s Top 10 Cancer Research Publications is a regular summary of the most interesting and impactful recent papers in cancer research. It is curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided by the authors.
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A. Fluckiger et al. Science 21 Aug 2020: Vol. 369, Issue 6506, pp. 936-942
“This report shows for the first time ‘molecular mimicry’ between microbial peptides and melanoma epitopes leading to T cell reactivity and associated with improved survival after PD1 immunotherapy.” Yardena Samuels, EACR Board Member
Summary of the findings
Our gut contains at least one thousand of different bacterial species. Bacteria can be infected by so-called phages, which are small virus-like objects that require bacterial hosts to replicate. In this Science paper, Fluckiger et al. describe the identification of a particular phage species, a Siphoviridae, that infects a class of intestinal bacteria called Enterococci. As it infects its bacterial host, this phage causes the expression of a protein that elicits a phage-specific immune response by the host immune system. Importantly, T cells that recognize a specific phage antigen also recognize cancer cells, as shown for laboratory mice as well as patients with lung or kidney cancer. Oncological patients carrying the Siphoviridae phage in their gut exhibit a better response to cancer immunotherapy than patients who lack them. Of note, the tumour antigen that is cross-reactive with the phage is non-mutated, both in mouse and human cancer cells. Fluckiger et al. also show that human T lymphocytes specific for non-mutated tumour antigens can be cross-reactive with microbial antigens. These results suggest that the microbiota can shape the immune repertoire, thus profoundly influencing anticancer immune responses that target non-mutated tumour-associated antigens.
Future impact of the findings
It is now established that prolonged treatments with broad-spectrum antibiotics abolish the efficacy of anticancer immunotherapies, supporting the idea that immunostimulatory bacteria must be present in the gut for an optimal treatment outcome. Indeed, it will be possible in the future to administer specific bacterial strains to cancer patients with the objective to ameliorate the control of tumours by the immune system. Probably, such immunostimulatory bacteria will be orally administered to patients in a personalized fashion so that they complement the microbial ecosystem and elicit the correct pattern of immune responses.
