Migrated T lymphocytes into malignant pleural effusions: an indicator of good prognosis in lung adenocarcinoma patients

Abstract

The presence of leukocyte subpopulations in malignant pleural effusions (MPEs) can have a different impact on tumor cell proliferation and vascular leakiness, their analysis can help to understand the metastatic microenvironment. We analyzed the relationship between the leukocyte subpopulation counts per ml of pleural fluid and the tumor cell count, molecular phenotype of lung adenocarcinoma (LAC), time from cancer diagnosis and previous oncologic therapy. We also evaluated the leukocyte composition of MPEs as a biomarker of prognosis. We determined CD4+ T, CD8+ T and CD20+ B cells, monocytes and neutrophils per ml in pleural effusions of 22 LAC and 10 heart failure (HF) patients by flow cytometry. Tumor cells were identified by morphology and CD326 expression. IFNγ, IL-10 and IL-17, and chemokines were determined by ELISAs and migratory response to pleural fluids by transwell assays. MPEs from LAC patients had more CD8+ T lymphocytes and a tendency to more CD4+ T and CD20+ B lymphocytes than HF-related fluids. However, no correlation was found between lymphocytes and tumor cells. In those MPEs which were detected >1 month from LAC diagnosis, there was a negative correlation between pleural tumor cells and CD8+ T lymphocytes. CXCL10 was responsible for the attraction of CD20+ B, CD4+ T and CD8+ T lymphocytes in malignant fluids. Concentrations of IL-17 were higher in MPEs than in HF-related effusions. Survival after MPE diagnosis correlated positively with CD4+ T and CD8+ T lymphocytes, but negatively with neutrophils and IL-17 levels. In conclusion, lymphocyte enrichment in MPEs from LAC patients is mostly due to local migration and increases patient survival.

CD4/CD8 Ratio of Pleural Effusion Is A Prognostic Predictor for Non-Small Cell Lung Cancer Patients Under Immune Checkpoint Inhibitor Treatments

“…3). In a previous study, Nieto et al reported CD20 + B lymphocytes account for 5.81% of all leukocytes in malignant pleural effusion 9 so our nding of 6.09% is reasonable for de ning "elevated" B cell ratio. Of the 17 patients, 5 had elevated B cell ratios in their initial pleural effusion analyses, and 4 of them were with type 1 and type 2 effusions.…”

“…Nieto et al reported that in patients after diagnosing malignant pleural effusion, their lymphocytes count in the pleural effusion is positively correlated with survival. CXCL10 helps attract lymphocytes in malignant effusion 9 . Accordingly, in patients with malignant pleural effusion, CD4/CD8 ratio of which is higher than the peripheral blood.…”

Prognostic role of immune microenvironment in pleural metastases from breast and lung adenocarcinomas

“…It seems that there is a tendency for metastatic pleural fluid to have higher levels of CD4 + cells compared to MM, and less important defect in recruiting CD8 + in the pleural cavity (2). Nieto and associates (21) showed that T cells are rather migrating than proliferating in the pleural cavity of lung cancer patients. Although in our study CD163 was not found to have a prognostic role, in a previous study CD163 higher counts in pleural fluid were associated with worse prognosis in 30 patients with lung cancer malignant pleural effusion (11).…”

Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells

“…In this work, for example, we show that apigenin suppressed the TNFα mediated rise in a potent tumor suppressor: CXCL10. While previous studies consistently that CXCL10 is up-regulated in normal vs. tumor tissue (76,77) this particular protein acts as the major tumor suppressor, evoked by IFN-γ treatment and somehow plays a role in the re-expression of MHC-1, PD-L1, the infiltration of anti-tumoral CD4(+) and CD8(+) T cells (78,79), NK cells, cytotoxic lymphocytes (CTLs) to the tumor to turn on immune surveillance and heighted survival odds in diverse human cancers (80)(81)(82). While the beneficial effects of apigenin in cancer are consistently reported, any compound that would turn off the CXCL9, -10, -11/CXCR3 axis could harm the host immunes system to destroy self-malignant tumor tissue (83).…”