GSE209807
Propranolol inhibit tumor growth through reducing T cell exhaustion
Recently, targeting or reinvigorating exhausted T cells have become the focus of cancer immunotherapy. Propranolol, a non-selection ß1 and ß2 adrenergic receptor blocker, or in combination with other drug, can inhibit the development of various tumors. Additionally, ß2-adrenergic receptor (ADRB2) signaling suppresses the effector function of CD8+ T cell. However, whether propranolol plays an anti-tumor role by directly inhibiting T cell exhaustion remains unclear. In this study, we found that Propranolol significantly inhibited the development of AOM/DSS-induced colorectal cancer, and reduced the exhaustion of infiltrating T cell in colorectal cancer tissues. The anti-tumor effect of propranolol was further determined by CT26, B16F10, and MC38 subcutaneous tumor models in vivo. Cell viability analysis showed that Propranolol concentration below 40 µM had no effect on the viability of CT26 colorectal cancer cells. We also found that propranolol treatment did not inhibit the growth of tumors in BALB/c nude mice. The above results indicated that Propranolol relied on T cells to exert its anti-tumor effects. Bioinformatics analysis highlighted that ADRB2 was positive correlated with T cell exhaustion signature in colon adenocarcinoma, pancreatic adenocarcinoma, testicular germ cell tumors, and glioblastoma multiforme patients using the website of GEPIA. Accordingly, Propranolol directly inhibited T cells exhaustion, and increased IFN-? secretion of CD4+ and CD8+ T cells in vitro. Collectively, propranolol plays anti-tumor role by directly inhibiting T cell exhaustion. Overall design: CT26 subcutaneous tumors mRNA profiles of Control and Propranolol tretment mice were generated by deep sequencing, in duplicate.