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Updated: Aug 2, 2025
Ex vivo Live Imaging of Lung Metastasis and Their Microenvironment
Published on: February 3, 2016
Expression of pannexin1 in lung cancer brain metastasis and immune microenvironment
Abstract:
Brain metastases are the most common central nervous system malignancy, and the leading cause of cancer-related deaths. Non-small cell lung carcinomas (NSCLC) comprise the most common cell of origin. Immunotherapy, particularly checkpoint inhibitors, has emerged as the standard of care for many patients with advanced lung cancer. Pannexin1 (PANX1) is a transmembrane glycoprotein that forms large-pore channels and has been reported to promote cancer metastasis. However, the roles of PANX1 in lung cancer brain metastases and tumor immune microenvironment have not been characterized. 42 patient-matched formalin-fixed paraffin-embedded tissue samples from lung carcinomas and the subsequent brain metastases were constructed into three tissue microarrays (TMAs). PANX1 and markers of tumor-infiltrating immune cells (CD3, CD4, CD8, CD68, and TMEM119) were assessed using immunohistochemistry and digital image analysis. The expression of PANX1 was significantly 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 peripheral 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.
Insights
Pannexin1 (PANX1) is elevated in non-small cell lung cancer brain metastases, correlating with fewer immune cells. Targeting PANX1 may improve immunotherapy effectiveness for brain metastasis.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Brain metastases are the most common CNS malignancy and a leading cause of cancer death, often originating from non-small cell lung carcinoma (NSCLC).
- Immune checkpoint inhibitors are a standard treatment for advanced lung cancer.
- Pannexin1 (PANX1) channels are implicated in cancer metastasis, but their role in lung cancer brain metastases and the tumor immune microenvironment is unknown.
Purpose of the Study:
- To investigate the expression and role of Pannexin1 (PANX1) in non-small cell lung carcinoma (NSCLC) brain metastases.
- To characterize the relationship between PANX1 expression and the tumor immune microenvironment in brain metastases.
Main Methods:
- Construction of tissue microarrays (TMAs) from 42 patient-matched primary lung carcinoma and brain metastasis samples.
- Immunohistochemistry and digital image analysis to assess PANX1 expression and tumor-infiltrating immune cells (CD3, CD4, CD8, CD68, TMEM119).
Main Results:
- PANX1 expression was significantly higher in brain metastases compared to primary lung tumors.
- High PANX1 levels in metastatic lung cancer cells inversely correlated with the infiltration of peripheral blood-derived macrophages.
Conclusions:
- PANX1 plays a role in the progression of metastatic NSCLC to the brain.
- Targeting PANX1 represents a potential therapeutic strategy to enhance the efficacy of immune checkpoint inhibitors in treating brain metastases.
