Native Soluble Carcinoembryonic Antigen Is Not Involved in the Impaired Activity of CD56^dim Natural Killer Cells in Malignant Pleural Effusion

Abstract

Background: Natural killer (NK) cells are lymphocytes of the innate immune system that play a crucial role in tumor immune surveillance. Accumulated data indicated that NK cells in the tumor microenvironment often display a suppressed function. However, the mechanism is not clear. Objective: In this study, the effects and relative mechanisms of malignant pleural effusion (MPE) from patients with lung cancer on NK cells were researched. Methods: MPE and peripheral blood (PB) samples were collected from patients with lung cancer. The cytotoxic activity of CD56^dim NK cells in PB and MPE mononuclear cells was analyzed by flow cytometry. Results: It was observed that the percentages of total NK cells and a CD56^dim NK subset in MPE reduced accompanying impaired cytotoxic activity compared with that in paired PB. Cell-free MPE treatment reduced both the proportion and cytotoxic activity of CD56^dim NK cells in PB from healthy donors. The suppression effects were not based on soluble carcinoembryonic antigen and the inhibitory cytokines interleukin-10 and transforming growth factor-β₁, but were dependent on the factor with a molecular weight >100 kDa. Conclusions: These results demonstrated that native soluble carcinoembryonic antigen does not suppress the activity of NK cells, and an unknown factor with a molecular weight >100 kDa plays a critical role in the impairment of CD56^dim NK cells in MPE, which might lead to tumor progression.

Impaired T cell function in malignant pleural effusion is caused by TGF‐β derived predominantly from macrophages

“…Preclinical studies support the principle that TGF‐β may participate in lung cancer progression in patients with MPE . Thus, targeting TGF‐β‐mediated signal transduction in tumors may provide a novel approach to controlling tumor growth .…”

“…Preclinical studies support the principle that TGF-b may participate in lung cancer progression in patients with MPE. 40 Thus, targeting TGF-b-mediated signal transduction in tumors may provide a novel approach to controlling tumor growth. 41 There are several pharmacological approaches available for blocking TGF-b signaling, including monoclonal antibodies, vaccines, antisense oligonucleotides and small molecule inhibitors.…”