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干扰素介导的体内小细胞肺癌和中肠类癌β2-微球蛋白的诱导。

Interferon-mediated in vivo induction of beta 2-microglobulin on small-cell lung cancers and mid-gut carcinoids.

作者信息

Funa K, Gazdar A F, Mattson K, Niiranen A, Koivuniemi A, Oberg K, Wilander E, Doyle A, Linnoila R I

出版信息

Clin Immunol Immunopathol. 1986 Oct;41(1):159-64. doi: 10.1016/0090-1229(86)90060-7.

DOI:10.1016/0090-1229(86)90060-7
PMID:3017623
Abstract

Selected neuroendocrine tumors, such as small cell lung cancer (SCLC), and neuroblastoma express markedly diminished class I major histocompatibility complex (MHC) antigens (HLA framework and beta 2-microglobulin, beta 2m). Another neuroendocrine tumor, mid-gut carcinoid, also expresses reduced beta 2m antigen as demonstrated herein. Antigen expression is greatly enhanced on SCLC cell lines by in vitro exposure to interferon (IFN). To determine whether IFN mediates similar effects in vivo, we examined by immunoperoxidase staining beta 2m expression in paraffin-embedded tumor tissue sections obtained from 4 SCLC and 7 mid-gut carcinoid patients before and after receiving partially purified human leukocyte IFN-alpha therapy. Before IFN treatment, 3/4 SCLC tumors and 5/7 mid-gut carcinoids did not express beta 2m. By contrast, all tumors showed considerable expression of beta 2m after IFN therapy. Induction of class I antigens on tumor cells deficient in such expression may be one mechanism by which IFN exerts antitumor effects. We believe this is the first report of in vivo induction of class I MHC antigens in epithelial tumor cells in humans.

摘要

某些神经内分泌肿瘤,如小细胞肺癌(SCLC)和神经母细胞瘤,表达明显减少的I类主要组织相容性复合体(MHC)抗原(HLA框架和β2微球蛋白,β2m)。本文证实,另一种神经内分泌肿瘤——中肠类癌,也表达减少的β2m抗原。通过体外暴露于干扰素(IFN),SCLC细胞系上的抗原表达大大增强。为了确定IFN在体内是否介导类似作用,我们通过免疫过氧化物酶染色检查了4例SCLC患者和7例中肠类癌患者在接受部分纯化的人白细胞IFN-α治疗前后石蜡包埋肿瘤组织切片中的β2m表达。在IFN治疗前,4例SCLC肿瘤中有3例、7例中肠类癌中有5例不表达β2m。相比之下,所有肿瘤在IFN治疗后均显示出β2m的大量表达。在缺乏此类表达的肿瘤细胞上诱导I类抗原可能是IFN发挥抗肿瘤作用的一种机制。我们认为这是关于人类上皮肿瘤细胞中I类MHC抗原体内诱导的首次报道。

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引用本文的文献

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Infiltrating T lymphocytes in the tumor microenvironment of small cell lung cancer: a state of knowledge review.小细胞肺癌肿瘤微环境中的浸润性 T 淋巴细胞:知识综述状态。
J Cancer Res Clin Oncol. 2022 Apr;148(4):881-895. doi: 10.1007/s00432-021-03895-x. Epub 2022 Jan 8.
2
Advances in Small-Cell Lung Cancer (SCLC) Translational Research.小细胞肺癌(SCLC)转化研究进展。
Cold Spring Harb Perspect Med. 2021 Apr 1;11(4):a038240. doi: 10.1101/cshperspect.a038240.
3
MHC class I and II antigen expression and interferon alpha treatment of human midgut carcinoid tumors.
人小肠类癌肿瘤的MHC I类和II类抗原表达及α干扰素治疗
World J Surg. 1994 Jul-Aug;18(4):481-6; discussion 486-7. doi: 10.1007/BF00353741.
4
Immunogenicity and immunosensitivity of ex vivo human carcinomas: interferon gamma and tumour necrosis factor alpha treatment of tumour cells potentiates their interaction with autologous blood lymphocytes.离体人癌的免疫原性和免疫敏感性:γ干扰素和肿瘤坏死因子α对肿瘤细胞的处理增强了它们与自体血淋巴细胞的相互作用。
Cancer Immunol Immunother. 1995 Oct;41(4):217-26. doi: 10.1007/BF01516996.
5
Auto-tumor recognition following in vitro induction of MHC antigen expression on solid human tumors: stimulation of lymphocytes and generation of cytotoxicity against the original MHC-antigen-negative tumor cells.在体外诱导实体人肿瘤细胞表达MHC抗原后进行自动肿瘤识别:刺激淋巴细胞并产生针对原始MHC抗原阴性肿瘤细胞的细胞毒性。
Cancer Immunol Immunother. 1989;28(1):17-21. doi: 10.1007/BF00205795.