淋巴细胞浸润人乳腺癌的特征:通过测量细胞因子分泌检测特异性免疫反应性。

D J Schwartzentruber, D Solomon, S A Rosenberg, S L Topalian
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引用次数: 95

摘要

19例原发性乳腺癌患者和其中9例患者的引流淋巴结(其中7例含有转移性肿瘤)用于培养肿瘤浸润淋巴细胞(TIL)。研究TIL的增殖、表型、细胞毒性和分泌细胞因子的能力对自体肿瘤的反应。原发乳腺肿瘤淋巴细胞在19个培养物中有15个增殖,65天内中位数为6.7 × 10(3)倍。对于9名患者中的8名,来自引流淋巴结的淋巴细胞在培养中增殖,49天内增殖的中位数为110倍。随着培养时间的推移,乳腺TIL以CD4+细胞为主,在63天(中位数)时,CD4+细胞为73%,CD8+细胞为21%。51 d时淋巴结淋巴细胞CD4+ 63%。在4小时51Cr释放试验中,TIL溶解不良。自体肿瘤的溶解发生在12例乳腺TIL中的1例和9例淋巴结培养中的1例。这种裂解很低(在效应:目标= 40:1时为15%)并且是非特异性的(非主要组织相容性复合物受限制)。将TIL与自体或异体肿瘤共培养24小时,检测细胞因子的分泌。用酶联免疫吸附法或放射免疫法测定培养上清液中的细胞因子。11例患者中有3例的TIL在受到自体肿瘤刺激时特异性分泌粒细胞巨噬细胞集落刺激因子、肿瘤坏死因子- α和干扰素- γ,而不是受到4 - 5例同种异体乳腺癌的刺激。细胞因子的分泌使得鉴定浸润乳腺癌的淋巴细胞具有特异性免疫反应性成为可能。这一发现将指导开发针对乳腺癌患者的新免疫疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Characterization of lymphocytes infiltrating human breast cancer: specific immune reactivity detected by measuring cytokine secretion.

Primary breast cancers from 19 patients and draining lymph nodes from nine of them (seven containing metastatic tumor) were used in growing tumor-infiltrating lymphocytes (TIL) in culture. TIL were studied for proliferation, phenotype, cytotoxicity, and the ability to secrete cytokines in response to autologous tumor. Lymphocytes from primary breast tumors proliferated in 15 of 19 cultures, a median of 6.7 x 10(3)-fold in 65 days. For eight of nine patients, lymphocytes derived from draining lymph nodes proliferated in culture, a median of 110-fold in 49 days. Breast TIL became predominantly CD4+ cells over time in culture and were 73% CD4+ and 21% CD8+ (means) at 63 days (median). Lymph node lymphocytes were 63% CD4+ at 51 days. TIL were poorly lytic in 4-hour 51Cr release assays. Lysis of autologous tumor occurred in only one of 12 breast TIL and one of nine lymph node cultures. This lysis was low (15% at effector:target = 40:1) and was nonspecific (non-major-histocompatibility-complex restricted). Cytokine secretion was tested by co-culturing TIL with autologous or allogeneic tumors for 24 hours. Cytokines were measured in culture supernatants by enzyme-linked immunosorbent assay or radioimmunoassay. TIL from three of 11 patients specifically secreted granulocyte macrophage-colony-stimulating factor, tumor necrosis factor-alpha and interferon-gamma when stimulated by autologous tumor and not by a panel of four to five allogeneic breast cancers. Cytokine secretion has made possible the identification of lymphocytes infiltrating breast cancers with specific immune reactivity. This finding will guide the development of new immunotherapies for patients with breast cancer.

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