Expression of pannexin1 in lung cancer brain metastasis and immune microenvironment

Brain metastases are the most common central nervous system malignan-cy, and the leading cause of cancer-related deaths. Non-small cell lung carcinomas (NSCLC) comprise the most common cell of or-igin. Immunotherapy, particularly checkpoint inhibitors, has emerged as the standard of care for many patients with advanced lung cancer. Pannexin1 (PANX1) is a transmembrane gly-coprotein that forms large-pore channels and has been reported to promote cancer me-tastasis. However, the roles of PANX1 in lung cancer brain metastases and tumor immune microenvironment have not been charac-terized. 42 patient-matched formalin-fixed paraffin-embedded tissue samples from lung carcinomas and the subsequent brain me-tastases were constructed into three tissue microarrays (TMAs). PANX1 and markers of tumor-infiltrating immune cells (CD3, CD4, CD8, CD68, and TMEM119) were assessed us-ing immunohistochemistry and digital image analysis. The expression of PANX1 was signifi-cantly higher in brain metastases than in their paired primary lung carcinoma. The high levels of PANX1 in lung carcinoma cells in the brain inversely correlated with infiltration of periph-eral blood-derived macrophages. Our findings highlight the role of PANX1 in the progression of metastatic NSCLC, and the potential thera-peutic approach of targeting PANX1 enhances the efficacy of immune checkpoint inhibitors in brain metastasis.