Recovery of CD8+ T-cell function during systemic chemotherapy in advanced ovarian cancer
Recovery of CD8+ T-cell function during systemic chemotherapy in advanced ovarian cancer
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DOI：
10.1158/0008-5472.can-04-3792
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发表时间：
2005-08-01
期刊：
影响因子：
11.2
通讯作者：
Tabi, Z
中科院分区：
文献类型：
--
作者：
Coleman, S;Clayton, A;Tabi, Z
免疫方法正在成为几种类型癌症的新治疗选择。然而，尽管患者产生有效的CD 8（+）T细胞应答的能力对于有效的抗肿瘤应答至关重要，但在进入免疫治疗的患者中，免疫活性和T细胞功能并未进行常规检测。本研究的目的是监测晚期癌症和化疗期间的T细胞功能。采用细胞因子流式细胞术对21例晚期卵巢癌（III-IV期）患者的CD 8（+）T细胞功能进行了评估，这些患者在体外用一组合成病毒肽（由泛高加索抗原表位组成）刺激42个PBMC样本。高水平（> 200单位/mL）Ca 125（肿瘤负荷和进展的标志物）患者的CD 8（+）T细胞应答显著低于低水平Ca 125患者（P = 0.0013）。在9例患者的纵向研究中，化疗与7例患者的Ca 125水平降低相关，7例患者的CD 8（+）T细胞功能改善或维持相关。在整个化疗过程后，9例缓解患者中有5例显示出有效的CD 8（+）T细胞应答，而9例进展患者中有4例显示出低或降低的T细胞应答，表明T细胞功能与临床应答之间存在相关性。我们的研究结果首次表明，CD 8（+）T细胞功能在晚期癌症中不会永久性抑制，成功的化疗与抗原特异性T细胞反应性的改善有关。我们认为，功能测定确定T细胞免疫活性可以优化癌症免疫治疗，提高临床成功的有价值的工具。
Immunologic approaches are emerging as new treatment options in several types of cancer. However, whereas the ability of patients to develop potent CD8(+) T-cell responses is crucial for efficient antitumor responses, immunocompetence and T-cell function are not tested routinely in patients entering inummotherapy. The objective of our study was to monitor T-cell function in advanced cancer and during chemotherapy. CD8(+) T-cell function of 21 patients with advanced ovarian cancer (stages III-IV) was assessed by cytokine flow cytometry following stimulation of 42 PBMC samples with a panel of synthetic viral peptides in vitro, consisting of pan-Caucasian epitopes. CD8(+) T-cell responses were significantly lower in patients with high levels (> 200 units/mL) of Ca125 (marker of tumor load and progression) than in those with low Ca125 levels (P = 0.0013). In longitudinal studies of nine patients, chemotherapy was associated with decreasing Ca125 levels in seven cases and also with improvement or maintenance of CD8(+) T-cell function in seven cases. After the full course of chemotherapy, five of nine patients in remission displayed potent CD8(+) T-cell responses, whereas four of nine patients in progression displayed low or decreasing T-cell responses, pointing toward a correlation between T-cell function and clinical response. Our results show for the first time that CD8(+) T-cell function is not permanently suppressed in advanced cancer and successful chemotherapy is associated with improved antigen-specific T-cell reactivity. We suggest that functional assays determining T-cell immunocompetence can be valuable tools for optimizing cancer immunotherapy for improved clinical success.