A Defined Commensal Consortium Elicits CD8 T cells and Anti-Cancer Immunity
By Dr.Katie E Golden, MD
As current research uncovers the critical role of the human microbiome in both infectious and inflammatory diseases, there is a natural curiosity about its potential for therapeutic intervention. Commensal bacteria have been shown to play a role in protection against infection and autoimmune disease, however we are still at the beginning of identifying those specific strains with the greatest impact on host physiology.
In a recently published study by Tanoue et.al. 1 , researchers make notable progress in isolating a group of bacterial species with important immunologic function. More specifically, they identified a specific cohort of bacterial strains that induce proliferation of IFN-𝛾 producing CD8 T cells in the intestine, which subsequently demonstrated a potent anti-infectious and anti-tumor effect without simultaneously inducing harmful inflammation. This is an important step forward in developing microbiome-based therapies.
To maximize the translational impact of their research, the investigators started with bacterial strains from human faecal samples. They fed these samples to germ-free mice, and measured the frequency of IFN𝛾 CD8 T cells (which are known to play an important role in fighting both infection and cancer). Through a series of subsequent analyses, there were able to isolate 11 bacterial strains that had a robust impact on CD8 T cell induction and proliferation. Intesterestingly, they also observed that this enhanced immunologic activity did not come with increased histological or transcription signs of colonic inflammation, which is potentially harmful to the host. They thus described how the bacternita signaled T cell induction, independent of innate immune pathways (through CD103+ dendritic cells and major histocompatibility class Ia molecules, to be more specific), to achieve this effect.
Perhaps the most exciting outcome of their study is the demonstrated efficacy in the treatment of both infectious and neoplastic disease. Mice that were colonized with these 11 bacterial strains, and subsequently infected with Listeria, exhibited enhanced clearance of the pathogenic bacteria (along with less clinical side effects of the infection, such as weight loss and colonic histological insult). This measurable therapeutic effect was also observed in the setting of cancer pathology. Researchers studied mice, again colonized with the selected bacterial strains, who were engrafted with cancer (adenocarincoma) cells. Not only did they observe increased efficacy of traditional immunotherapy agents (immune checkpoint inhibitors) in these mice, but they also had significantly suppressed tumor growth even in the absence of these specific therapies.
Their work is an important first step in the development of microbiome therapeutics, and furthermore demonstrates the potential for its application to a broad spectrum of disease.
- Tanoue T, Morita S, Plichta DR, Skelly AN, Suda W, Sugiura Y, Narushima S, Vlamakis H, Motoo I, Sugita K, Shiota A, Takeshita K, Yasuma-Mitobe K, Riethmacher D, Kaisho T, Norman JM, Mucida D, Suematsu M, Yaguchi T, Bucci V, Inoue T, Kawakami Y, Olle B, Roberts B, Hattori M, Xavier RJ, Atarashi K, Honda K. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature. 2019 Jan;565(7741):600-605.