Expression of pannexin1 in brain metastases derived from lung cancer

Brain metastases (BMs) are the leading cause of cancer-related deaths, comprise the majority of central nervous system malignancies, and widely originate from non-small lung carcinomas (NSCLC). Immunotherapy, particularly checkpoint inhibitors, has emerged as the standard of care for most patients with advanced lung cancer. Pannexin1 (PANX1) is a transmembrane glycoprotein that forms large-pore channels and has been reported to promote tumorigenesis in metastatic cancers. However, the roles of PANX1 in lung cancer-associated brain metastases and tumor-infiltrating lymphocytes have not been identified. Forty-two patient-matched formalin-fixed paraffin-embedded tissue samples from lung carcinomas and subsequent brain metastases were constructed into two master-tissue microarrays (TMAs). PANX1, PD-L1, and tumor-infiltrating immune cells (CD3+, CD4+, CD8+, and CD68+) were assessed using immunohistochemistry and digital image analysis (QuPath software). The expression of PANX1 was significantly higher in brain metastases than paired primary lung carcinoma. Strikingly, the level of PANX1 in lung carcinoma cells in the brain correlated negatively with the infiltration density of blood-derived macrophages. Our findings highlight the role of PANX1 in the progression of metastatic NSCLC, and the potential therapeutic approach of targeting PANX1 enhances the efficacy of immune checkpoint inhibitors in brain metastasis.