Islas-Vazquez Lorenzo, Aguilar-Cazares Dolores, Galicia-Velasco Miriam, Rumbo-Nava Uriel, Meneses-Flores Manuel, Luna-Rivero Cesar, Lopez-Gonzalez Jose Sullivan
Lung Cancer Laboratory, Department of Chronic-Degenerative Diseases, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col Seccion XVl, Mexico City CP 14080, Mexico.
Neumo-Oncology Clinic, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col Seccion XVl, Mexico City CP 14080, Mexico.
Biology (Basel). 2020 Nov 5;9(11):376. doi: 10.3390/biology9110376.
Cytokines, key contributors to tumorigenesis, are mediators between inflammatory immune or nonimmune and cancer cells. Here, IL-6 production by tumor cells was assessed in a cohort of patients with lung adenocarcinoma treated with conventional therapy. IL-6 levels and neutrophil-lymphocyte ratio (NLR) or systemic immune-inflammation index (SII) markers were evaluated. Changes in pro- and anti-inflammatory cytokines, HMGB1 concentration, and CD4+ and CD8+ T-lymphocyte populations and their subpopulations were investigated. IL-6 expression was detected immunohistochemically in lung adenocarcinoma biopsies. Cytokines were quantified using the cytometric bead array, and TGF-β and HMGB-1 through ELISA. Clinical parameters were collected to assess NLR and SII. CD4+ and CD8+ T-lymphocytes and naïve, memory, and effector subpopulations were quantified by flow cytometry. The data obtained were associated with patients' median overall survival (OS). IL-6 showed the highest increase, probably because the lung adenocarcinoma cells produced IL-6. Patients with higher OS had lower NLR and SII from the third cycle of chemotherapy. Patients with lower OS had significantly lower percentages of CD8+ T-lymphocyte and its effector subpopulations, with a concomitant increase in the naïve subpopulation. This study suggests that in addition to the known inflammatory markers, IL-6, CD8+ T-lymphocytes and their effector and naïve subpopulations could be useful as predictive markers in lung adenocarcinoma.
细胞因子是肿瘤发生的关键促成因素，是炎症性免疫或非免疫细胞与癌细胞之间的介质。在此，我们评估了一组接受传统治疗的肺腺癌患者肿瘤细胞产生白细胞介素-6（IL-6）的情况。评估了IL-6水平、中性粒细胞与淋巴细胞比值（NLR）或全身免疫炎症指数（SII）标志物。研究了促炎和抗炎细胞因子、高迁移率族蛋白B1（HMGB1）浓度以及CD4⁺和CD8⁺T淋巴细胞群体及其亚群的变化。通过免疫组织化学检测肺腺癌活检组织中的IL-6表达。使用细胞计数珠阵列对细胞因子进行定量，并通过酶联免疫吸附测定法对转化生长因子-β（TGF-β）和HMGB-1进行定量。收集临床参数以评估NLR和SII。通过流式细胞术对CD4⁺和CD8⁺T淋巴细胞以及幼稚、记忆和效应亚群进行定量。所获得的数据与患者的中位总生存期（OS）相关。IL-6升高最为明显，这可能是因为肺腺癌细胞产生了IL-6。从化疗第三个周期起，总生存期较长的患者NLR和SII较低。总生存期较短的患者CD8⁺T淋巴细胞及其效应亚群的百分比显著降低，同时幼稚亚群增加。这项研究表明，除了已知的炎症标志物外，IL-6、CD8⁺T淋巴细胞及其效应和幼稚亚群可作为肺腺癌的预测标志物。
