upregulates the immune inhibitory receptor in colorectal cancer cells via the activation of ALPK1.

is a Gram-negative oncobacterium that is associated with colorectal cancer. The molecular mechanisms utilized by to promote colorectal tumor development have largely focused on adhesin-mediated binding to the tumor tissue and on the pro-inflammatory capacity of . However, the exact manner in which promotes inflammation in the tumor microenvironment and subsequent tumor promotion remains underexplored. Here, we show that both living and sterile conditioned medium promote CXCL8 release from the intestinal adenocarcinoma HT-29 cell line. We determined that the observed pro-inflammatory effect was ALPK1-dependent in both HEK293 and HT-29 cells and that the released molecule had characteristics that match those of the pro-inflammatory ALPK1 ligand ADP-heptose or related heptose phosphates. In addition, we determined that not only promoted an ALPK1-dependent pro-inflammatory environment but also other species such as , and generated similar effects, indicating that ADP-heptose or related heptose phosphate secretion is a conserved feature of the genus. By performing transcriptional analysis of ADP-heptose stimulated HT-29 cells, we found several inflammatory and cancer-related pathways to be differentially regulated, including DNA mismatch repair genes and the immune inhibitory receptor . Finally, we show that stimulation of HT-29 cells with resulted in an ALPK1-dependent upregulation of . These results aid in our understanding of the mechanisms by which can affect tumor development and therapy and pave the way for future therapeutic approaches.