When mice with PDA were treated with antibiotic regimens targeted at the most prominent bacterial species, their tumor burden was reduced by about 50% and showed slowed tumor progression. These antibiotic treatments also led to an increase in the number of T cells within PDA tissue and a decrease in immune-suppressing cells. There was, in particular, an increase in the differentiation of macrophages and CD4 and CD8 T cells.
The authors postulated that the dysbiosis stimulated by particular bacteria can lead to PDA progression by promoting peri-tumoral immune suppression. Mice with PDA treated with antibiotics and subsequently re-populated with PDA-associated bacteria had this protective effect reversed and tumor progression was enhanced. These mice also expressed higher levels of PD-1, which, when targeted with anti-PD-1 treatments along with antibiotics, led to synergistic reduction in the size of PDA tumors.
This study also evaluated mechanisms that may explain how the bacteria associated with pancreatic cancer could promote tumorigenesis. PRRs were up-regulated in mice with PDA, which may promote oncogenesis by suppressing the immune system. These same mice who were treated with antibiotics subsequently had lower levels of PRRs.
In the future, targets of drug development may be within the microbiome, and may combat dysbiosis or alter the interaction between the microbiome and cancer cells. The Pushalkar et al study, furthermore, raises the question of whether there could be a role for antibiotics in patients at high risk for PDA. Antibiotics are, however, notoriously over-prescribed, especially in the United States, so judiciousness would be critical.
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