Desmoplasia: a possible immunosuppressive microenvironment in colorectal cancer 2302078

Abstract

Abstract Introduction Colorectal cancer (CRC) is the third most frequently diagnosed cancer and the leading cause of cancer-related deaths in Mexico. The complexity of this cancer and its nonspecific symptoms compromise patient diagnosis and prognosis. A feature of CRC is the formation of Desmoplasia, a reaction of the connective tissue surrounding the tumor in which excess fibrous tissue is produced. This fibrous tissue, formed by fibroblasts called cancer-associated fibroblasts (CAFs), is an important component of the tumor microenvironment in CRC and can affect tumor growth and spread, as well as treatment response. The desmoplastic stromal tissue (DS) expresses α-SMA, fibronectin, and tumor cells in epithelial-mesenchymal transition (EMT) tissue (EpCAM, Pancytokeratin, vimentin, E-Cadherin), and its role in poor or benign prognosis remains controversial. Interestingly, most studies on the role of DS in CRC have relied on histological examination, without assessing molecular expression of tissue markers that could provide more detailed information on the tumor microenvironment. Moreover, whether high desmoplasia in CRC is associated with an immunosuppressive environment is unknown. Methods We analyzed 90 CRC patients with distinct staging by IHQ and IF, the expression of molecular markers expressed in the DS, including a-SMA, vimentin, PD-L1, PD-L2, and markers for innate lymphoid cells, to determine the association between the expression of desmoplastic stromal markers and EMT tumor tissue markers, highlighting the clinical stage, molecular markers expression, and patient survival. Results We found a significant association between PD-L1/PD-L2 expression and the DS, as well as the recruitment of ILC1s with strong stromal marker expression, suggesting an immunosuppressive phenomenon in these patients. Interestingly, α-SMA- and PD-L2-positive tissues were associated with poor survival in CRC. Conclusion A high desmoplastic reaction may be associated with an immunosuppressive microenvironment in CRC. Funding Source DGAPA-PAPIIT-UNAM IV200425. Sociedad Mexicana de Oncología 2024 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)