Background/Aims. IL17-producing Th17 represent a distinct subset of T-cells. The link between IL-17a and the colorectal cancer (CRC) microenvironment has been widely accepted. However, the role of IL-17a in epithelial cell apoptosis, autophagy, mucinosis, ultrastructural changes, and their potential correlations with CRC remains unclear. Materials and Methods. Out of 2890 patients with CRC, 200 were divided into four groups (stage I-IV) and 50 into non-CRC/healthy/control. We investigated the relationship between IL-17a, apoptosis, autophagy, and mucinosis in patients with stage I-IV CRC ( in vitro/vivo ). In addition to many (para)clinical assessments, IL-17a load in blood and the tumor microenvironment (TME) in patients with CRC were assessed. To exam- ine these associations, the effect of IL-17a on CRC cells was evaluated using qPCR, Western blotting, ELISA, bioluminescence, flow cytometry, and immunohistochemistry (IHC), and ultrastructural changes in the colonic epithelia were assessed by scanning and transmission electron microscopy. Results. IL-17a is overexpressed in stage I–IV in the TME and in stage III–IV in the blood of patients with CRC. IL-17a upregulated apoptosis (caspases, cytochrome c (CYC), higher Bax:Bcl2 ratio), autophagy (SIRT1 and LC3), and the cell cycle (TP53, APC-1) and downregulated B3GALNT2 and mucins and led to morphological and nuclear changes in CRC epithelia. Conclusions. IL-17a is abundantly expressed in the CRC microenvironment, and IL-17a- IL-17aR interactions play a critical role in the control of apoptosis and mucinosis. The observed remarkable association of IL-17a and apoptosis in adenocarcinoma provides valuable insight into the clinical implications of Th17/IL-17 in CRC. © 2025 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

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