Abstract 2420: Exploring associations between the IL4 pathway and colorectal cancer risk in in vivo models and clinical records

Abstract

Abstract We have previously demonstrated that inhibition of the IL4 pathway limits metastatic potential in colorectal cancers and have postulated that the type II IL4 receptor could serve as a potential target in risk assessment and treatment. Here we expand on these findings through in vivo mouse studies and retrospective patient analysis. To elucidate how colorectal cancers may use the IL4 pathway to grow and infiltrate surrounding tissue, we performed two in vivo studies independently targeting IL4ra in myeloid and intestinal epithelial tissues. Mice with a deleted allele of IL4ra and a floxed allele of IL4ra were crossed with either a line expressing a myeloid-specific Cre (LysM Cre) or an intestinal epithelial-specific Cre (Villin Cre). Our results indicate that myeloid-expressed IL4ra facilitates tumorigenesis but is not a significant contributor to later growth. In contrast, epithelial IL4ra significantly contributes to tumor number and size, but had little effect on the observed number of aberrant crypt foci, an early indicator of colon cancer. We hypothesized that effects of atypical IL4 activity could also be observed in the medical record. Atopic diseases such as asthma and eczema are characterized by an overabundance of IgE, a protein regulated by the IL4 pathway. Using Vanderbilt University Medical Center’s SD Discover program, we obtained de-identified records for patients diagnosed with at least stage II colorectal carcinoma between 2005 and 2015. We then stratified patients by metastatic progression. Patients who were diagnosed with asthma prior to age sixty were significantly less likely to develop an advanced form of colorectal cancer and at reduced risk of metastatic disease or recurrence. This may be a result of medication prescribed for atopic disease such as inhalers and corticosteroids and we are performing further analyses to test these hypotheses. Citation Format: Jacob Beckstead, Jack Petros, Kunaal Mehrotra, Barbara Fingleton. Exploring associations between the IL4 pathway and colorectal cancer risk in in vivo models and clinical records [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2420.