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Interleukin‐2 reverses CD8+ T cell exhaustion in clinical malignant pleural effusion of lung cancer

Malignant pleural effusion (MPE) is a poor prognostic sign for cancer patients, whereas the functional condition of MPE CD8+ T cells is unknown. Intracavitary immunotherapy with interleukin (IL)‐2 has been proven effective in controlling MPE. To elucidate the underlying mechanism, 35 lung cancer (LC) patients with MPE and 12 healthy donors were included in this study. For the IL‐2 therapy experiments, after draining partial MPE, we treated 14 patients by administrating IL‐2 (3 or 5 × 106 U in 50 ml saline) into the thoracic cavity. Before and after IL‐2 treatment (40‐48 h), the MPE and peripheral blood (PB) were obtained from the subjects. PB from healthy volunteers was collected as control. The expression of programmed cell death 1 (PD‐1), granzyme B (GzmB), interferon (IFN)‐γ and the proliferation were analysed in CD8+ T cells from MPE and PB. The CD8+ T cells in the MPE of LC patients showed lowest GzmB, IFN‐γ and proliferation but highest PD‐1 expression, compared with that in PB of LC patients and healthy donors. IL‐2 treatment reduced the expression of PD‐1, increased the expression of GzmB and IFN‐γ and enhanced the proliferation of CD8+ T cells in MPE. In addition, IL‐2 treatment reduced carcino‐embryonic antigen (CEA) level in MPE. These results indicate that MPE CD8+ T cells exhibit exhaustion phenotype which can be reversed by IL‐2 therapy.