Gut instinct.

Top Line: Gut bacteria play an important role in priming immune cells.

The Study: In fact, several species of bacteria are associated with improved outcomes in patients treated with immune checkpoint inhibitors (ICI). But what is it about these bacterial species that elicit anti-tumor immune responses? This study homed in on a bacteriophage protein called TMP1 contained in a specific line of Enterococcus hirae that resulted in tumor control of certain types of mouse sarcomas treated with cyclophosphamide. When non-E. hirae cells were transfected with a TMP1 phase or engineered to produce TMP1, they produced similar anti-tumor effects. To what was TMP1 priming the immune system, though? A specific protein over-expressed in some mouse tumor cell lines ended up being highly homologous to TMP1. When looking at a human cohort of patients, those who had fecal enterococci carrying the TMP phage or those who had tumor expression of a TMP-homologous tumor antigen had better treatment outcomes with immune checkpoint inhibition. There are two important things about this study. First, it shows us a mechanism by which microbiota can induce immune cross-reactivity with tumor antigens. And, second, it demonstrates that bacteriophages can be transferred to different gut bacteria and used to modulate anti-tumor immune response.

TBL: Antigens from gut bacteriophages  can mimic those of tumor antigens to prime anti-tumor immunity. | Fluckiger, Science 2020

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