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诊断为晚期肺癌患者的细胞因子、EGF 和淋巴细胞亚群之间的关联。

Associations among cytokines, EGF and lymphocyte subpopulations in patients diagnosed with advanced lung cancer.

机构信息

Clinical Research Direction, Center of Molecular Immunology, 216 St., Corner 15, PO Box 16040, Atabey, Playa, Havana, Cuba.

Biochemical Department, Instituto de Ciencias Básicas Y Preclínicas "Victoria de Girón", Havana, Cuba.

出版信息

Cancer Immunol Immunother. 2021 Jun;70(6):1735-1743. doi: 10.1007/s00262-020-02823-1. Epub 2021 Jan 2.

Abstract

Aging is considered the single most significant risk factor for the majority of common malignances including lung cancer. Together immunosenescence, changes occurring with aging in the immune system, and inflammaging, characterizes by a chronic, subclinical accumulation of pro-inflammatory factors, are suggested to stand at the origin of most of the diseases of the elderly, such as cancer. The aim of this study was to determine associations among lymphocyte subpopulations, pro-inflammatory cytokines and epidermal growth factor (EGF) in patients diagnosed with non-small cell lung cancer (NSCLC). Forty-six advanced NSCLC patients were enrolled. Sixteen patients with newly diagnosed and before treatment and 30 patients after first-line platinum-based chemotherapy. Peripheral blood subpopulations were studied by flow cytometry and serum concentrations of soluble factors by ELISA. The frequency of naïve CD4 T cells, naïve B cells and central memory CD8 T cells were significantly lower in NSCLC patients after chemotherapy, while effector memory CD4 T cells and terminally differentiated CD8 T cells were significantly higher. IL-1β and TNFα significantly correlated among them before and after platinum-based chemotherapy. Terminally differentiated T cells expressing CD57 significantly correlated with TNFα and IL-1β. For the first time, associations between EGF serum levels and terminally differentiated CD4 T cells, and memory B cells were detected. This study confirms the association among terminally differentiated lymphocytes and pro-inflammatory cytokines in patients diagnosed with lung cancer, reinforcing the interconnection between terminally differentiated lymphocytes and pro-inflammatory cytokines. Clinical trial registration number: RPCEC00000205, http://registroclinico.sld.cu/.

摘要

衰老是大多数常见恶性肿瘤(包括肺癌)的最重要单一危险因素。共同的免疫衰老,随着年龄的增长在免疫系统中发生的变化,以及炎症衰老,其特征是慢性、亚临床积累促炎因子,被认为是大多数老年人疾病(如癌症)的起源。本研究旨在确定非小细胞肺癌(NSCLC)患者淋巴细胞亚群、促炎细胞因子和表皮生长因子(EGF)之间的关联。共纳入 46 例晚期 NSCLC 患者。其中 16 例为初诊未治疗患者,30 例为一线铂类化疗后患者。采用流式细胞术研究外周血亚群,采用 ELISA 法检测血清可溶性因子浓度。化疗后 NSCLC 患者的幼稚 CD4 T 细胞、幼稚 B 细胞和中央记忆 CD8 T 细胞频率显著降低,而效应记忆 CD4 T 细胞和终末分化 CD8 T 细胞显著升高。IL-1β和 TNFα在化疗前后显著相关。表达 CD57 的终末分化 T 细胞与 TNFα和 IL-1β显著相关。本研究首次检测到 EGF 血清水平与终末分化 CD4 T 细胞和记忆 B 细胞之间的关联。本研究证实了肺癌患者终末分化淋巴细胞与促炎细胞因子之间的关联,强化了终末分化淋巴细胞与促炎细胞因子之间的联系。临床试验注册号:RPCEC00000205,http://registroclinico.sld.cu/。

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