Investigation of the role of the immune receptor CD300e in a mouse model of obesity-associated colorectal cancer

Colorectal cancer (CRC) is one of the most frequently diagnosed malignant neoplasms and its diagnosis is associated with a high mortality rate. The progression of this malignancy is significantly influenced by immune escape mechanisms, therefore immune checkpoint inhibitor therapy has emerged as a promising treatment strategy. Recent in vitro evidence has brought attention to the inhibitory role of CD300e in antigen presentation, proposing its potential as a novel immune checkpoint receptor. The present study aims to investigate the in vivo relevance of CD300e by employing a constitutive CD300e KO mouse model of CRC. Given the well-recognized correlation between CRC and obesity, we designed an experimental framework to mimic obesity-associated CRC in our animal model. Following the experimental timeline, we conducted morphological, molecular and immunophenotypic analyses. Our findings unravel a profound influence of diet on CD300e-deleted mice to tumorigenesis. Standard diet-fed KO mice exhibit a better anti-tumor response compared to WT animals, as testified by smaller tumors, lower expression of genes associated to metastasis and invasiveness, and increased expression of IFN-γ. This effect is impaired under high-fat diet, where no differences are observed between the two mouse strains. Overall, data suggest that CD300e acts as an immune checkpoint, but the influence of the diet requires further investigations.