Chen Hong, Liakou Chrysoula I, Kamat Ashish, Pettaway Curtis, Ward John F, Tang Derek Ng, Sun Jingjing, Jungbluth Achim A, Troncoso Patricia, Logothetis Christopher, Sharma Padmanee
Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2729-34. doi: 10.1073/pnas.0813175106. Epub 2009 Feb 6.
Cytotoxic lymphocyte antigen-4 (CTLA-4) blockade is an active immunotherapeutic strategy that is currently in clinical trials in cancer. There are several ongoing trials of anti-CTLA-4 in the metastatic setting of prostate cancer patients with reported clinical responses consisting of decreases in the prostate specific antigen (PSA) tumor marker for some patients. Immunologic markers that correlate with these clinical responses are necessary to guide further development of anti-CTLA-4 therapy in the treatment of cancer patients. We recently reported that CD4(+) inducible co-stimulator (ICOS)(hi) T cells that produce interferon-gamma (IFN-gamma) are increased in the peripheral blood and tumor tissues of bladder cancer patients treated with anti-CTLA-4 antibody. Here we present data from the same clinical trial in bladder cancer patients demonstrating a higher frequency of CD4(+)ICOS(hi) T cells and IFN-gamma mRNA levels in nonmalignant prostate tissues and incidental prostate tumor tissues removed at the time of radical cystoprostatectomy. Our data suggest immunologic markers that can be used to monitor prostate cancer patients who receive anti-CTLA-4 therapy and indicate that the immunologic impact of anti-CTLA-4 antibody can occur in both tumor and nonmalignant tissues. These data should be taken into consideration for evaluation of efficacy as well as immune-related adverse events associated with anti-CTLA-4 therapy.
细胞毒性淋巴细胞抗原4（CTLA-4）阻断是一种目前正在癌症临床试验中的主动免疫治疗策略。有几项正在进行的针对前列腺癌患者转移情况的抗CTLA-4试验，报告的临床反应包括部分患者前列腺特异性抗原（PSA）肿瘤标志物降低。与这些临床反应相关的免疫标志物对于指导抗CTLA-4疗法在癌症患者治疗中的进一步发展是必要的。我们最近报告称，在用抗CTLA-4抗体治疗的膀胱癌患者的外周血和肿瘤组织中，产生干扰素-γ（IFN-γ）的CD4（+）诱导性共刺激分子（ICOS）（高表达）T细胞增加。在此，我们展示来自同一膀胱癌患者临床试验的数据，这些数据表明在根治性膀胱前列腺切除术时切除的非恶性前列腺组织和偶然发现的前列腺肿瘤组织中，CD4（+）ICOS（高表达）T细胞的频率更高，且IFN-γ mRNA水平更高。我们的数据提示可用于监测接受抗CTLA-4治疗的前列腺癌患者的免疫标志物，并表明抗CTLA-4抗体的免疫影响可在肿瘤组织和非恶性组织中均发生。在评估抗CTLA-4治疗的疗效以及与免疫相关的不良事件时，应考虑这些数据。
