Combinatorial effect of autoimmunity and infection as a potential etiology factor for early onset of gastric cancer development

Recently, gastric cancer (GC) demographics have shifted to include younger patients, especially with an increase in diagnoses of young women. While the basis of the shift is unknown, it is believed the change may be due to increased rates of autoimmunity, which remains more prevalent in women. Chronic Helicobacter pylori (Hp) infection is the greatest risk factor for the development of GC, but infection rates have decreased in industrialized nations, thus gastric autoimmunity may be contributing to the shift in demographics. We hypothesize that infection and autoimmunity synergize to advance inflammatory tumorigenesis. To investigate this, we infected CTLA4 knockdown (CTLA4KD) mice, which develop GC in an autoimmunity-dependent manner, with Hp. We observed increased inflammation within the gastric mucosa and sub-mucosa including tertiary lymphoid structures within the mucosa in infected CTLA4KD mice, compared to infected wild-type and non-infected controls. In addition, there appears to be more invasive growths in Hp infected CTLA4KD mice. On the other hand, CTLA4KD mice have decreased Hp load in stool samples, measured by qPCR, which indicates autoimmunity may inhibit colonization or promote clearance of Hp within parts of the gastrointestinal tract other than the gastric mucosa. Preliminary data suggests that combinatorial gastric autoimmunity and Hp infection may cooperate to promote gastric inflammatory tumorigenesis that leads to early GC development.