Dadmarz R D, Ordoubadi A, Mixon A, Thompson C O, Barracchini K C, Hijazi Y M, Steller M A, Rosenberg S A, Schwartzentruber D J
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cancer J Sci Am. 1996 Sep-Oct;2(5):263-72.
To search for tumor-specific in vitro reactivity by lymphocytes derived from patients with ovarian carcinoma.
Tumor-infiltrating lymphocytes (TIL) were derived from primary or metastatic solid tumors and tumor-associated lymphocytes (TAL) were derived from ascites from 13 patients with ovarian cancer. TIL or TAL were cultured for approximately 30 to 60 days and studied for phenotype, cytotoxicity, and cytokine secretion in response to autologous tumor stimulation.
Twenty-nine bulk TIL or TAL cultures were successfully established from 10 patients using various culture conditions. Thirteen cultures were predominantly CD4+ and 16 were mainly CD8+. In contrast to reports by others, none of the cultures tested were specifically lyric for autologous tumor. Five predominantly CD4+ bulk TIL (from four patients) preferentially secreted tumor necrosis factor-alpha and granulocyte macrophage-colony stimulating factor when stimulated with autologous tumor and not when stimulated by autologous Epstein Barr virus-B cells, fibroblasts, peripheral blood mononuclear cells, or allogeneic HLA matched or mismatched stimulators. This cytokine secretion was found to be MHC class-II restricted in three patients because it was inhibited by the anti-MHC class-II antibody IVA12 and the HLA-DR specific antibody L243.
We believe these data are the first to suggest that tumor reactive CD4+ lymphocytes exist in some ovarian cancer patients. This finding may be useful in the development of novel immunotherapies for these patients.
寻找卵巢癌患者来源的淋巴细胞在体外的肿瘤特异性反应性。
肿瘤浸润淋巴细胞（TIL）来自原发性或转移性实体瘤，肿瘤相关淋巴细胞（TAL）来自13例卵巢癌患者的腹水。TIL或TAL培养约30至60天，并研究其对自体肿瘤刺激的表型、细胞毒性和细胞因子分泌情况。
使用不同培养条件从10例患者中成功建立了29个TIL或TAL大量培养物。13个培养物主要为CD4 +，16个主要为CD8 +。与其他人的报告相反，所测试的培养物中没有一个对自体肿瘤具有特异性杀伤作用。5个主要为CD4 +的大量TIL（来自4例患者）在用自体肿瘤刺激时优先分泌肿瘤坏死因子-α和粒细胞巨噬细胞集落刺激因子，而在用自体爱泼斯坦-巴尔病毒-B细胞、成纤维细胞、外周血单个核细胞或同种异体HLA匹配或不匹配的刺激物刺激时则不分泌。在3例患者中发现这种细胞因子分泌受MHC-II类限制，因为它被抗MHC-II类抗体IVA12和HLA-DR特异性抗体L243抑制。
我们认为这些数据首次表明在一些卵巢癌患者中存在肿瘤反应性CD4 +淋巴细胞。这一发现可能有助于为这些患者开发新的免疫疗法。
