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免疫检查点表达作为非小细胞肺癌患者的预后生物标志物候选物。

Immune checkpoint expression as prognostic biomarker candidates in non-small cell lung carcinoma patients.

机构信息

Department of Clinical Research, Hospital de Câncer de Pernambuco (HCP), Recife, Brazil.

Programa de Pós-graduação em Medicina Translacional, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.

出版信息

J Surg Oncol. 2024 Sep;130(4):919-928. doi: 10.1002/jso.27763. Epub 2024 Jul 7.

DOI:10.1002/jso.27763
PMID:38973141
Abstract

BACKGROUND

Cancer immunotherapy has had an important role in oncologic therapeutics for patients with non-small cell lung cancer (NSCLC) using checkpoint inhibitors. We will explore the possible prognosis biomarker candidates such as: soluble OX40 (sOX40), OX40L (sOX40L), Glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR), and their ligand (GITRL), 4-1BB or tumor necrosis factor receptor superfamily 9 (TNFRS9) and inducible T cell co-stimulator (ICOS) in peripheral blood of NSCLC patients.

METHODS

Fifty-eight patients were diagnosed with advanced NSCLC between January 2019 and March 2020.

RESULTS

High sOX40 and low s4-1BB levels in smokers compared non-smoker NSCLC patients. Lower sOX40L levels were found in the male than female (p < 0.05). High sOX40 and sGITRL in stage III compared to the stage IV (p < 0.05). With follow-up at 21.4 months, 44.1% and 91.1% were alive in the sGITR and sGITR groups, respectively (p = 0.02), and 73.3% and 27.7% were alive in the sGITRL and sGITRL groups, respectively (p = 0.02). At 22 months, 38.7% and 92.3% were alive in the sOX40L and sOX40L groups, respectively (p = 0.01).

CONCLUSION

sGITR, sGITRL, and sOX40L levels were potential prognostic biomarkers and could have an important role as new targets of immunotherapy in NSCLC patients. sGITR, sGITRL, sOX40L, and sOX40 levels were associated with smoking, sex, stage, and age in NSCLC.

摘要

背景

癌症免疫疗法在使用检查点抑制剂治疗非小细胞肺癌(NSCLC)患者的肿瘤治疗中发挥了重要作用。我们将探索外周血中可能的预后生物标志物候选物,如:可溶性 OX40(sOX40)、OX40L(sOX40L)、糖皮质激素诱导的肿瘤坏死因子受体家族相关受体(GITR)及其配体(GITRL)、4-1BB 或肿瘤坏死因子受体超家族 9(TNFRS9)和诱导型 T 细胞共刺激分子(ICOS)在 NSCLC 患者中的作用。

方法

2019 年 1 月至 2020 年 3 月期间,诊断出 58 例晚期 NSCLC 患者。

结果

与非吸烟者相比,吸烟者外周血中 sOX40 水平较高,s4-1BB 水平较低。男性外周血中 sOX40L 水平低于女性(p<0.05)。与 IV 期相比,III 期患者外周血中 sOX40 和 sGITRL 水平较高(p<0.05)。随访 21.4 个月后,sGITR 组和 sGITR 组的生存率分别为 44.1%和 91.1%(p=0.02),sGITRL 组和 sGITRL 组的生存率分别为 73.3%和 27.7%(p=0.02)。22 个月时,sOX40L 组和 sOX40L 组的生存率分别为 38.7%和 92.3%(p=0.01)。

结论

sGITR、sGITRL 和 sOX40L 水平可能是潜在的预后生物标志物,作为 NSCLC 患者免疫治疗的新靶点具有重要作用。sGITR、sGITRL、sOX40L 和 sOX40 水平与吸烟、性别、分期和年龄有关。

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