Effect of interleukin-7 on the anti-tumor function of CD8(+) T cells in patients with non-small cell lung cancer

Abstract

Objective: To investigate the effect of interleukin (IL)-7 on anti-tumor activity of CD8(+) T cells in non-small cell lung cancer (NSCLC) patients. Methods: Twenty-seven NSCLC patients and ten healthy controls were included from Zhengzhou Central Hospital between January 2017 and July 2017. Plasma, peripheral blood mononuclear cells (PBMCs), and bronchial alveolar lavage fluid (BALF) (both tumor site and non-tumor site) were collect from NSCLC patients, while plasma and PBMCs were also collected from healthy controls. IL-7 level and IL-7 receptor α (CD127) mRNA relative expression was measured. Purified CD8(+) T cells and primary NSCLC cells were stimulated with recombinant IL-7. Cellular proliferation, cytokines secretion, and protein expression in IL-7 signaling pathway were investigated. Direct/indirect contact coculture system of CD8(+) T cells and primary NSCLC cells was also used to assess the cytolytic and noncytolytic activity after IL-7 stimulation. Results: Plasma IL-7 level was significantly reduced in NSCLC patients compared with normal controls[1 731 (1 364, 2 536) vs 2 686 (1 692, 4 786) ng/L, P=0.023). IL-7 level in BALF isolated from tumor site was also remarkably down-regulated compared with non-tumor site in NSCLC patients[1 045 (562, 1 550) vs 1 599 (1 166, 2 107) ng/L, P=0.006 9). There was no statistical difference of CD127 mRNA between the two groups. Recombinant IL-7 stimulation did not affect cellular proliferation and cytokines production in primary NSCLC cells, however, remarkably increased cellular proliferation, interferon (IFN)-γ/tumor necrosis factor (TNF)-α secretion, and signal transducers and activators of transcription 5 (STAT5) phosphorylation and suppressor of cytokine signaling 3 (SOCS3) expression of CD8(+) T cells from NSCLC patients. IL-7 stimulation also significantly enhanced the cytolytic and noncytolytic function of CD8(+) T cells on primary NSCLC cells. Conclusion: IL-7 enhances anti-tumor activity of CD8(+) T cells in NSCLC patients.