Downregulation of CD132 in Colonic Adenomas and Cancer Is Associated with γδ T-Cell Loss, Increased Apoptosis, and Microsporidia Infection.

Background/Objectives: Colorectal cancer commonly develops through an adenoma-carcinoma sequence, but the immune alterations accompanying this transition remain incompletely understood. Because we previously observed reduced γδ T cells, increased apoptosis, and frequent microsporidia infection in colorectal cancer, we investigated whether similar changes are already present in colonic adenomas. Methods: We studied 55 subjects, including 30 patients with colonic adenomas, 10 with colorectal cancer, and 15 healthy controls. Peripheral blood T-cell subsets and apoptosis were assessed by flow cytometry, tissue expression of IL-7, CD127, and CD132 was analyzed by RT-PCR, and microsporidia were detected in colonic tissues by immunofluorescence and real-time PCR. Results: γδ T cells were progressively reduced in colonic adenomas and further decreased in colorectal cancer, while apoptosis of both αβ and γδ T cells increased compared with healthy subjects. Tissue expression of CD132 was significantly downregulated in adenomas and colorectal cancer, whereas IL-7 expression was increased, particularly in adenomatous tissue, consistent with a compensatory mechanism attempting to preserve T-cell homeostasis despite reduced CD132 expression. Microsporidia prevalence rose from healthy controls to patients with colonic adenomas and colorectal cancer, and CD132 expression was more markedly reduced in microsporidia-positive colonic adenoma and cancer tissues. Conclusions: These findings indicate that altered IL-2 receptor-related signaling, γδ T-cell depletion, and increased apoptosis are already present at the adenoma stage and are associated with microsporidial infection. This pattern suggests a potential link between parasitic colonization and local immune dysfunction during colorectal tumorigenesis.