Bol Kalijn F, Aarntzen Erik H J G, Hout Florentien E M In 't, Schreibelt Gerty, Creemers Jeroen H A, Lesterhuis W Joost, Gerritsen Winald R, Grunhagen Dirk J, Verhoef Cornelis, Punt Cornelis J A, Bonenkamp Johannes J, de Wilt Johannes H W, Figdor Carl G, de Vries I Jolanda M
Department of Tumor Immunology; Radboud Institute for Molecular Life Sciences; Radboud University Medical Center; Nijmegen, The Netherlands; Department of Medical Oncology; Radboud University Medical Center; Nijmegen, The Netherlands.
Department of Tumor Immunology; Radboud Institute for Molecular Life Sciences; Radboud University Medical Center; Nijmegen, The Netherlands; Department of Medical Oncology; Radboud University Medical Center; Nijmegen, The Netherlands; Department of Radiology and Nuclear Medicine; Radboud University Medical Center; Nijmegen, The Netherlands.
Oncoimmunology. 2015 Jun 5;5(1):e1057673. doi: 10.1080/2162402X.2015.1057673. eCollection 2016.
Melanoma patients with regional metastatic disease are at high risk for recurrence and metastatic disease, despite radical lymph node dissection (RLND). We investigated the immunologic response and clinical outcome to adjuvant dendritic cell (DC) vaccination in melanoma patients with regional metastatic disease who underwent RLND with curative intent. In this retrospective study, 78 melanoma patients with regional lymph node metastasis who underwent RLND received autologous DCs loaded with gp100 and tyrosinase and were analyzed for functional tumor-specific T cell responses in skin-test infiltrating lymphocytes. The study shows that adjuvant DC vaccination in melanoma patients with regional lymph node metastasis is safe and induced functional tumor-specific T cell responses in 71% of the patients. The presence of functional tumor-specific T cells was correlated with a better 2-year overall survival (OS) rate. OS was significantly higher after adjuvant DC vaccination compared to 209 matched controls who underwent RLND without adjuvant DC vaccination, 63.6 mo vs. 31.0 mo ( = 0.018; hazard ratio 0.59; 95%CI 0.42-0.84). Five-year survival rate increased from 38% to 53% ( < 0.01). In summary, in melanoma patients with regional metastatic disease, who are at high risk for recurrence and metastatic disease after RLND, adjuvant DC vaccination is well tolerated. It induced functional tumor-specific immune responses in the majority of patients and these were related to clinical outcome. OS was significantly higher compared to matched controls. A randomized clinical trial is needed to prospectively validate the efficacy of DC vaccination in the adjuvant setting.
尽管进行了根治性淋巴结清扫术(RLND),但患有区域转移性疾病的黑色素瘤患者仍有很高的复发和转移性疾病风险。我们调查了接受RLND且有治愈意图的区域转移性疾病黑色素瘤患者接受辅助性树突状细胞(DC)疫苗接种后的免疫反应和临床结果。在这项回顾性研究中,78例接受RLND的区域淋巴结转移黑色素瘤患者接受了负载gp100和酪氨酸酶的自体DC,并对皮肤试验浸润淋巴细胞中的功能性肿瘤特异性T细胞反应进行了分析。研究表明,区域淋巴结转移黑色素瘤患者接受辅助性DC疫苗接种是安全的,71%的患者诱导产生了功能性肿瘤特异性T细胞反应。功能性肿瘤特异性T细胞的存在与更好的2年总生存率(OS)相关。与209例未接受辅助性DC疫苗接种而仅接受RLND的匹配对照相比,辅助性DC疫苗接种后的OS显著更高,分别为63.6个月和31.0个月(P = 0.018;风险比0.59;95%CI 0.42 - 0.84)。五年生存率从38%提高到了53%(P < 0.01)。总之,对于RLND后有复发和转移性疾病高风险的区域转移性疾病黑色素瘤患者,辅助性DC疫苗接种耐受性良好。它在大多数患者中诱导产生了功能性肿瘤特异性免疫反应,且这些反应与临床结果相关。与匹配对照相比,OS显著更高。需要进行一项随机临床试验来前瞻性地验证DC疫苗接种在辅助治疗中的疗效。