Immune Surveillance Tissue Antigen Profiling in Advanced Ovarian Cancer

Patrick J. Stiff , Ronald K. Potkul , Girish Venkataraman , Payal Sojitra , Maureen L. Drakes
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引用次数: 2

Abstract

Aim

A knowledge of tumor-related antigens associated with survival of patients with ovarian cancer could contribute toward the development of tests for early diagnosis and could provide targets for the design of novel immunotherapy for advanced ovarian cancer. We conducted a pilot immunohistochemical study to determine a group of antigens in ovarian tumor masses that correlate with survival.

Methods

We studied T-cell subsets and tumor antigens on 69 cases of paraffin-embedded patient blocks to determine if any correlated with survival in this disease. These were identified by staining for CD3, CD8, FoxP3, New York esophageal-1 (NY-ESO-1), melanoma-associated antigen (MAGE) A, cyclin E, and intercellular adhesion molecule-1 (ICAM-1) antigens in tissue when using specific antibodies.

Results

Study patients had a median age of 58 years and an overall survival of 31%. Infiltrating CD3+ T cells correlated with improved survival of patients (P = .002, log-rank test). The frequency of cyclin E, ICAM-1, CD8, and FoxP3 expressing cells were not statistically associated with survival. MAGE-A was expressed in 10 (45%) of 22 whole-tissue sections studied, and this expression correlated with decreased survival (P = .03, log-rank test). The presence and frequency of FoxP3 infiltrating suppressor T cells was associated with high-stage disease (P = .02, χ2 test; P = .03, Wilcoxon test).

Conclusions

The significance of CD3 T cells in tumor tissue may be primarily associated with an active antitumor immune response. MAGE-A family members may represent successful antigens for immunotherapeutic targeting in ovarian cancer.

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晚期卵巢癌的免疫监测组织抗原谱分析
了解与卵巢癌患者生存相关的肿瘤相关抗原有助于开发早期诊断测试,并可为设计晚期卵巢癌的新型免疫疗法提供靶点。我们进行了一项试点免疫组织化学研究,以确定卵巢肿瘤肿块中与生存相关的一组抗原。方法对69例石蜡包埋患者块的t细胞亚群和肿瘤抗原进行研究,以确定它们是否与该疾病的生存相关。当使用特异性抗体时,通过对组织中的CD3、CD8、FoxP3、New York esophageal-1 (NY-ESO-1)、黑色素瘤相关抗原(MAGE) A、细胞周期蛋白E和细胞间粘附分子-1 (ICAM-1)抗原进行染色鉴定。研究患者的中位年龄为58岁,总生存率为31%。浸润CD3+ T细胞与患者生存率提高相关(P = 0.002, log-rank检验)。cyclin E、ICAM-1、CD8和FoxP3表达细胞的频率与生存率无统计学相关性。研究的22个全组织切片中有10个(45%)表达MAGE-A,其表达与生存率降低相关(P = 0.03, log-rank检验)。FoxP3浸润抑制性T细胞的存在和频率与高分期疾病相关(P = 0.02, χ2检验;P = .03, Wilcoxon检验)。结论cd3t细胞在肿瘤组织中的作用可能主要与肿瘤免疫反应有关。MAGE-A家族成员可能代表卵巢癌免疫治疗靶向的成功抗原。
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