High PANX1 Expression Leads To Neutrophil Recruitment And Formation of A High Adenosine Immunosuppressive Tumor Microenvironment In Triple-Negative Breast Cancer

Abstract High adenosine levels are an important characteristic of the tumor microenvironment (TME) in triple-negative breast cancer (TNBC). Pannexin 1 (PANX1) can release intracellular ATP to the extracellular space and elevate extracellular ATP (exATP) levels under physiological conditions. We performed public database bioinformatics analysis, surgical specimen histological validation, RNA sequencing, and exATP/extracellular adenosine (exADO) assays in vitro and in vivo to reveal the role of PANX1 in regulating the immune microenvironment of TNBC. Our results revealed that PANX1 was highly expressed and acted as a poor prognostic factor in TNBC. The PANX1 expression level was positively correlated with exATP and exADO levels in the TNBC TME. PANX1 promoted infiltration of tumor-associated neutrophils (TANs) through exATP, and TANs highly expressed ENTPD1 (CD39) / NT5E (CD73). This study suggests that high PANX1 expression could promote TAN accumulation and adenosine production in the TNBC TME which have been shown to induce local immunosuppression.