ALBERT

Description: Objective: In the previous study, we found a high proportion expression of HO-1 and Foxp3 in tumor tissues of patients with DLBCL result in a poor prognosis, and there is a positive correlation between HO-1 and Foxp3. Activation of A2aR not only increases the number of Treg cells but also directly enhances their immunosuppression to tumor cells. on the other hand, A2aR on the surface of tumor cells was also induced, considering a positive correlation between HO-1 and Foxp3, it is hypothesized that activation of A2aR in tumor cells results in upregulated HO-1 expression. And HO-1 play a crucial role in the maintenance and survival of tumor cells in the tumor immune microenvironment, so this study aimed to prove that adenosine activates the A2aR receptor of tumor cells to upregulate the expression of HO-1. Further investigating the regulation and mechanism of the interaction between A2aR and HO-1, elucidating the role of A2aR receptor activation in the immune microenvironment of patients with DLBCL. Methods: Multi-color immunohistochemical staining (mIHC) was performed on paraffin sections of clinical cases with DLBCL to make a quantitative analysis the expression of biomarkers of the immune microenvironment, K-M survival curve and Log-Rank test were used for statistical analysis. Oci-ly10 and Oci-ly19 cell lines were used as the DLBCL cell model, were treated with A2aR receptor agonist, adenosine and NECA. NECA-pretreated cells were treated by anticancer drugs Cisplatin and Vincristine (VCR). Western blot, CCK8 test and FACS were performed on measure the expression of HO-1, cell viability and apoptosis, respectively. NOD-SCID mouse bearing Oci-ly10 cells were established in to investigate the effect of induced HO-1 by A2aR activation on tumor growth inhibition and drug-resistance in vivo. Results: The results of multicolor immunohistochemistry showed that lower expression of HO-1, Foxp3 and PD-L1 and higher expression of CD8 obtained a higher overall survival(p0.05). There was a positive correlation between the HO-1 and Foxp3 cells among the tumor microenvironment markers (p