Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination

被引：56

作者：

Bol, Kalijn F. ^{[1
,2
]}

Aarntzen, Erik H. J. G. ^{[1
,2
,3
]}

in 't Hout, Florentien E. M. ^{[1
,4
]}

Schreibelt, Gerty ^{[1
]}

Creemers, Jeroen H. A. ^{[1
]}

Lesterhuis, W. Joost ^{[1
,5
]}

Gerritsen, Winald R. ^{[2
]}

Grunhagen, Dirk J. ^{[6
]}

Verhoef, Cornelis ^{[6
]}

Punt, Cornelis J. A. ^{[7
]}

Bonenkamp, Johannes J. ^{[4
]}

de Wilt, Johannes H. W. ^{[4
]}

Figdor, Carl G. ^{[1
]}

de Vries, I. Jolanda M. ^{[1
,2
]}

机构：

[1] Radboud Univ Nijmegen, Dept Tumor Immunol, Radboud Inst Mol Life Sci, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Dept Med Oncol, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Dept Radiol & Nucl Med, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Dept Surg Oncol, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[5] Univ Western Australia, Dept Med & Pharmacol, Crawley, Australia

[6] Erasmus MC Canc Inst, Dept Surg Oncol, Rotterdam, Netherlands

[7] Univ Amsterdam, Acad Med Ctr, Dept Med Oncol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

来源：

ONCOIMMUNOLOGY | 2016年 / 5卷 / 01期

关键词：

adjuvant therapy; dendritic cell; immunotherapy; melanoma; vaccination; AMERICAN JOINT COMMITTEE; LYMPH-NODE DISSECTION; HIGH-RISK; T-CELLS; THERAPEUTIC LYMPHADENECTOMY; COMPLETE RESECTION; IMMUNE-RESPONSES; IMMUNOTHERAPY; CD4(+); IPILIMUMAB;

D O I：

10.1080/2162402X.2015.1057673

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 (p = 0.018; hazard ratio 0.59; 95% CI 0.42-0.84). Five-year survival rate increased from 38% to 53% (p < 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.

引用

页数：8

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