CTLA-4、PD-1和PD-L1在小细胞肺癌外周血中的分布及临床意义

BACKGROUND AND OBJECTIVE: The aim of this study is to explore cytotoxic T lymphocyte associated antigen 4 (CTLA-4), programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) distribution and clinical value in liquid biopsy (such as blood) of small cell lung cancer (SCLC) patients. METHODS: A total of 60 healthy and 290 chemotherapy-naive patients with SCLC were recruited. Venous blood samples were collected prior to chemotherapy (baseline) and after the second cycle of chemotherapy (2(nd) cycle), and flow cytometry was used to analyze the level of CTLA-4, PD-1 or PD-L1 with or without CD3, CD4, CD8 or CD25. Immunocytochemical method was used to detect PD-L1 expression in SCLC cell line H446. RESULTS: Cells of CTLA-4(+) and PD-1(+) in SCLC peripheral blood were (1.56±1.24)% and (8.07±3.97)%; there is no significant difference between CD3(+)CTLA-4(+) and CD4(+)CTLA-4(+), (4.87±5.18)% and (3.85±2.60)%, but show lower expression than CD3(+)PD-1(+) and CD4(+)PD-1(+) (26.63±9.04)% and (20.79±9.41)%, respectively. However, the level of CD4(+)CD25(+)CTLA-4(+) cells were remarkably higher in SCLC than that in control, (7.09±5.09)% vs (1.91±1.27)%, P < 0.001 and CD8(+)PD-1(+) cells were less in SCLC than that in control, (11.47±5.85)% vs (22.56±4.21)%, P < 0.001, both of which were not associated with age, sex, smoke or disease stage. Level of CD4(+)CD25(+)CTLA-4(+) cells and CD8(+)PD-1(+) cells was dropped (5.11±2.60)% vs (6.94±4.91)% and (8.74±3.39)% vs (11.48±5.91)% after 2(nd) cycle compare to that at baseline (P < 0.000, 1). Neither the level of CD4(+)CD25(+)CTLA-4(+) nor CD8(+)PD-1(+) cells before or after treatment was related to progression-free disease or overall survival of patients. Although PD-L1 was highly expressed in H446 cell cytoplasm and membrane, it was rarely found in peripheral blood. CONCLUSION: The data we presented here showed that CTLA-4 was highly expressed in regulatory T cells and PD-1 decreased in CD8(+) T cells in peripheral blood of SCLC patients, suggesting their unique mechanisms involved in immune regulation. CD4(+)CD25(+)CTLA-4(+) level changed after treatment implies its potential role in predicting treatment efficacy.