Elevated CD38 expression characterizes impaired CD8⁺ T cell immune response in metastatic pleural effusions

Highly coordinated signaling following TCR stimulation triggers activation and subsequent differentiation of T cells. CD38 is a major mammalian nicotinamide adenine dinucleotide (NAD)⁺ glycohydrolase expressed on T cells, and appears to be an important modulator of T cell response in tumor models. However, the functional involvement of CD38 in T cells remains largely unknown. Therefore, we characterize the presence and function of CD38 in lymphocytes from metastatic pleural effusions (MPE). Of note, a significant accumulation of CD38⁺CD8⁺ T cells was observed in MPE compared with matched peripheral blood mononuclear cells (PBMC). Moreover, PD-1 expression was significantly increased within the CD38⁺CD8⁺ T cell fraction compared to CD38^- counterparts. We further showed decreased amounts of IFNγ and TNFα production together with reduced mitochondrial membrane potential in CD38⁺CD8⁺ T cells. Indeed, the impaired capacity of secreting IFNγ and TNFα by CD38⁺CD8⁺ T cells was likely due to damaged mitochondrial function. Taken together, we have identified a subset of CD38⁺CD8⁺ T cells in MPE, which possessed exhausted phenotype accompanied by altered mitochondrial metabolism.