Spatial Proximity of Tumor Infiltrating Immune Cells Uncovers a Novel Insight in Pulmonary Lymphoepithelial Carcinoma

Abstract Pulmonary lymphoepithelial carcinoma (LEC) is a rare type of lung cancer. Though the clinical outcomes of patients with LEC are better than those for patients with other types of lung cancer, tumors frequently recur. Evidence has indicated that the immune microenvironment factors may predict outcome of cancer therapy; however, the composition of immune microenvironment in LEC remains largely unknown. We investigated the association between the immune microenvironment of LEC by using multiplex immunohistochemical staining. The densities of each tumor-infiltrating immune cell type and the amount of infiltrating immune cells spatially proximal to the closet tumor cell were analyzed. Although there was no significant correlation between the clinical outcome of LEC and the density of each tumor-infiltrating immune cell type, we found that the amount of CD4 + T lymphocyte proximal to tumor positively trended to longer disease-free survival in LEC. Additionally, the PD-L1 tumor proportion score was highly correlated with the amount of CD8 + T lymphocyte proximal to tumor, suggesting that immunotherapy might be beneficial for LEC patients. The spatial proximity of tumor-infiltrating immune cell measurement is useful for investigating the tumor-immune cells interaction. The spatial proximity of tumor-infiltrating CD4 + T lymphocytes might serve as a good prognostic factor for LEC.