Intra-tumoral infiltration of adipocyte facilitates the activation of antitumor immune response in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy that is characterized by an immuno-suppressive microenvironment. The immune suppression in PDAC is largely driven by heterogeneous stromal and tumor cells. However, how adipocyte in the tumor microenvironment (TME) is related to the immune cell infiltration in PDAC has rarely been published. We identified adipocytes by performing bioinformatics analyses, and explored the clinical outcomes and TME characters in PDAC with different levels of adipocyte infiltration. Interestingly, in contrast to adiposity, high adipocyte infiltration in the TME was related to significantly increased median overall survival and a lower total tumor mutational burden. Functionally, high adipocyte infiltration was associated with the immune response, particularly with the abundant cytokine infiltration in PDAC samples. Moreover, adipocyte infiltration in the TME was positively associated with anticancer signatures in the immune microenvironment. Immunohistochemistry and RT-PCR were performed with PDAC tissue sam-ples from our center to study the expression of adipocytes in PDAC. The mature adipocytes were strongly associated with the immune composition and prognosis of patients with PDAC. Primary adipocytes were isolated from mice to construct a PDAC transplantation tumor model. In vivo experiments showed that adipocytes elicited increased CD8+ T cell infiltration and potent antitumor activity in tumor-bearing mice. Overall, we innovatively found that adipocytes facilitated the antitumor immune response in the TME by performing mouse experiments and analyzing PDAC samples. This study provides a new perspective on the activation of the immune micro -environment in PDAC.

Automated summary

This study discovered the important role of adipocytes in pancreatic ductal adenocarcinoma (PDAC), as high levels of adipocyte infiltration were associated with enhanced immune response and lower tumor mutational burden. Through mouse experiments and analysis of PDAC samples, the study provides a new perspective on the activation of the immune microenvironment in PDAC.