Herein, we show that neutrophils bind to DPEP1-expressing CRC cells and that a lack of DPEP1 in carcinogen-induced colonic neoplasia results in adenocarcinomas (ACAs) that exhibit many of the features of MSI-H cancers, including a reduction in mismatch repair gene expression and an influx of CD8+ T cells into the tumor proper. Here, DPEP1 is linked to adenocarcinoma.