Interleukin-2 Reverses CD8~+ T Cell Exhaustion In Clinical Malignant Pleural Effusion Of Lung Cancer

With the deterioration of air pollution,the incidence of respiratory diseases has been increasing year by year.As a respiratory malignancy,the morbidity and mortality of lung cancer(LC)are in the first place among all domestic malignants.Malignant pleural effusion(MPE),as a sign of violation of the pleura,announced a poor prognostic for cancer patients,nevertheless the functional condition of MPE CD8~+ T cells is still unknown.Intracavity perfusion with interleukin(IL)-2 can effectively control MPE.To clarify the underlying mechanism,35 lung cancer(LC)patients with MPE and 12 healthy blood donors were included in this study.For the IL-2 therapy experiments,after draining away MPE,we treated 14 patients by perfusing IL-2(3 or 5 ? 106 U in 50 ml saline)into the thoracic cavity.Before and after IL-2 infusion(40-48 h),the MPE and peripheral blood(PB)were collected from the subjects.PB from healthy donors was obtained as control.The expression of programmed cell death 1(PD-1),interferon(IFN)-?,granzyme B(GzmB),and the proliferation were analyzed in CD8~+ T cells from MPE and PB.In the MPE the CD8~+ T cells showed lowest IFN-?,GzmB and proliferation but highest PD-1 expression,compared with that in PB of LC patients and healthy volunteers.IL-2 treatment can reduce the expression of PD-1,increase the expression of IFN-? and GzmB and enhance the proliferation of CD8~+ T cells in MPE.Furthermore,IL-2 treatment also reduced carcino-embryonic antigen(CEA)level in MPE.These results illuminated that MPE CD8~+ T cells exhibit exhaustion phenotype which can be reversed by IL-2 therapy.Our study elucidated the mechanisms of IL-2 control of MPE,and provided theoretical basis for the treatment of pleural effusion with IL-2.