TGFβ2 Promotes the Construction of Fibrotic and Immunosuppressive Tumor Microenvironment in Pancreatic Adenocarcinoma: A Comprehensive Analysis.

Abstract

Pancreatic adenocarcinoma (PAAD) was characterized by dense fibrotic stroma and immunosuppressive tumor microenvironment (TME). TGFβ signaling pathways are highly activated in human cancers. However, the role of TGFβ2 in TME of PAAD remains to be elucidated. In this study, we showed that TGFβ2 was expressed at a relatively high level in PAAD tissues or cancer cells. Moreover, its high expression predicted unfavorable prognosis. In PAAD, gene set enrichment analysis showed that TGFβ2 correlated positively with leukocyte transendothelial migration, but negatively with aerobic metabolism, including oxidative phosphorylation. Results in Tumor and Immune System Interaction Database showed that TGFβ2 correlated with the infiltration of tumor-associated macrophages (TAMs), which could be attributed to that TGFβ2 promote CCL2 expression in PAAD. Moreover, correlation analysis showed that TGFβ2 could trigger cancer-associated fibroblasts (CAFs) activation in PAAD. The drug sensitivity analysis may indicate that patients with TGFβ2 high expression have higher sensitivity to chemotherapeutics, but the sensitivity to targeted drugs is still controversial. TGFβ2 could promote expansion of CAFs and infiltration of TAMs, thus participating in the construction of a fibrotic and immunosuppressive TME in PAAD. Targeting TGFβ2 could be a promising therapeutic approach, which needs to be elucidated by clinical and experimental evidences.