In the ongoing development of cancer immunotherapy, as well as our still developing understanding of the human immune system, there’s always been a bit of massive elephant in the room. The thing about human bodies is that they’re not just human cells, but also consist of trillions of bacteria that mostly live in the intestines. What effect these bacteria have on the immune system’s functioning and from there on immunotherapies was recently investigated by [Tariq A. Najar] et al., with an article published in Nature.
The relevant topic here is that of antigenic mimicry, involving microbial antigens that resemble self-antigens. Since these self-antigens are a crucial aspect of both autoimmune diseases and cancer immunotherapy there is considerable room for interaction with their microbial mimics. Correspondingly these mimics can have considerable negative as well as positive implications, ranging from potentially triggering an autoimmune condition to hindering or boosting cancer immunotherapy.
In this study mice were used to investigate the effect of such microbial interference, in particular focusing on immune checkpoint blockade (ICB), which refers to negative feedback responses within the immune system that some cancers use to protect themselves. In some immunotherapy patients ICB inhibiting using e.g. anti programmed cell death protein (anti-PD-1) treatment does not provoke a response for some reason.
For the study mice had tumors implanted and the effect of a particular microbe (segmented filamentous bacteria, SFB) on it studied, with the presence of it markedly improving the response to anti-PD-1 treatment due to anti-gens expressed by SFB despite the large gut-skin distance. Whether in humans similar mechanisms play a similarly strong role remains to be investigated, but it offers renewed hope that cancer immunotherapies like CAR T-cell immunotherapy will one day make cancer an easily curable condition.