Exploratory Pilot Study to Characterize the Immune Landscapes of Malignant Pleural Effusions and Their Corresponding Primary Tumors from Patients with Breast Carcinoma and Lung Adenocarcinoma

Background Malignant pleural effusion (MPE) is a frequent complication of advanced malignancies. In this pilot study, we characterized the immune landscapes of MPEs, compared them to their primary tumor (PT) samples from breast carcinoma (BC) and lung adenocarcinoma (LADC), and tested the utility of multiplexed image technology in cytological samples. Methods We evaluated the immune contexture of 6 BC and 5 LADC MPEs and their PTs using 3 multiplex immunofluorescence panels. We explored the associations between sample characteristics and pleural effusion–free survival. Results No MPE samples had positive programmed death-ligand 1 (PD-L1) expression in malignant cells, although 3 of 11 PTs were PD-L1-positive (more than 1% expression in malignant cells). Overall, in LADC samples, cluster of differentiation 3 (CD3)+ T cells and CD3+CD8+ cytotoxic T cells predominated (median percentages for MPEs vs. PTs: 45.6% vs. 40.7% and 4.7% vs. 6.6%, respectively) compared with BC. CD68+ macrophages predominated in the BC samples (medians for MPEs 61.2% vs. PTs for 57.1%) but not in the LADC samples. Generally in PTs, CD3+CD8+ forkhead box P3+ T cells and the median distances from the malignant cells to CD3+CD8+Ki67+ and CD3+ programmed cell death protein 1+ T cells correlated to earlier MPE after PT diagnosis. Conclusions The immune cell phenotypes in the MPEs and PTs were similar within each cancer type but different between BC vs. LADC. An MPE analysis can potentially be used as a substitute for a PT analysis, but an expanded study of this topic is essential.