SPORE in Skin Cancer

近年来，黑色素瘤的发病率急剧上升，但没有任何治疗方法可以提高大多数不可切除转移性疾病患者的总体生存率。匹兹堡大学癌症研究所（UPCI）黑色素瘤和皮肤癌项目（MSCP）将继续开展一项卓越研究专业项目（SPORE），以提高我们对癌症进展的分子和免疫机制的理解，并验证晚期黑色素瘤和皮肤T细胞淋巴瘤（CTCL）个性化治疗的预后和预测性生物标志物。在我们的4个项目中，1个是在上一个资助期继续进行的，3个新项目是在上一个资助期进行的发展研究中衍生出来的；之前的《孢子》项目中有1个将继续使用独立的ROI资金。我们高度整合的方法利用了黑色素瘤、肿瘤学、皮肤病学、免疫学、生物统计学、生物信息学、机器学习、基因组学、蛋白质组学和生物标志物发现方面的互补专业知识，以测试对改善皮肤癌治疗结果至关重要的假设。无论临床结果如何，这些项目也将产生迫切需要的机制数据，为开发新的治疗策略和途径提供信息，通过这些策略和途径监测复发和进展。我们的4个项目将评估：(1)与伊匹单抗和干扰素（IFN）辅助治疗相关的促炎反应和免疫抑制标志物的预后和预测价值（利用东方肿瘤合作小组领导的辅助试验）；(2)一种工程化的3抗原树突状细胞疫苗和IFN¿对转移性黑色素瘤患者的促进作用；(3) vemurafenib调节IFN¿2b免疫治疗转移性黑色素瘤患者的安全性和有效性；(4)黑色素瘤和CTCL患者的全新个性化微针疫苗接种技术。行政核心(A)协调临床研究，并提供整个孢子的科学和财政监督。生物标本中心(B)位于UPCI免疫监测和细胞产品实验室，所有组织库、生物标本处理和免疫分析都在这里进行。生物统计学核心(C)和信息学核心(D)分别支持所有数据分析和管理项目。我们将继续征求、审查和资助职业发展和发展研究项目的申请，这些申请在之前的资助期内导致了本申请中一个新的完整项目的设计（项目3）。

The incidence of melanoma has risen dramatically in recent years, but no therapy has improved overall survival for the majority of patients with unresectable metastatic disease. The University of Pittsburgh Cancer Institute (UPCI) Melanoma and Skin Cancer Program (MSCP) will continue to conduct a Specialized Program of Research Excellence (SPORE) to improve our understanding of molecular and immunologic mechanisms of cancer progression and to validate prognostic and predictive biomarkers for personalized treatment of advanced melanoma and cutaneous T cell lymphoma (CTCL). Of our 4 Projects, 1 is continued from the prior funding period, and 3 new projects have been derived from developmental research conducted in the last period; 1 of the prior SPORE projects will be continued with independent ROI funding. Our highly integrated approach leverages complementary expertise in melanoma, oncology, dermatology, immunology, biostatistics, bioinformatics, machine learning, genomics, proteomics, and biomarker discovery to test hypotheses central to the improvement of therapeutic outcome in skin cancers. Regardless of clinical outcomes, these Projects will also generate urgently needed mechanistic data to inform development of new therapeutic strategies and pathways through which to monitor relapse and progression. Our 4 Projects will evaluate: (1) the prognostic and predictive value of the pro-inflammatory response and markers of immune suppression in relation to ipilimumab and interferon (IFN)¿ adjuvant therapy (leveraging an Eastern Cooperative Oncology Group-led adjuvant trial); (2) an engineered, 3-antigen dendritic cell vaccine and IFN¿ boost in patients with metastatic melanoma; (3) the safety and efficacy of vemurafenib modulation of immunotherapy with IFN¿2b in patients with metastatic melanoma; and (4) an entirely new personalized microneedle vaccination technology in patients with melanoma and CTCL. The Administrative Core (A) coordinates the clinical research and provides scientific and fiscal oversight of the entire SPORE. The Biospecimen Core (B) is housed in the UPCI Immunologic Monitoring and Cellular Products Laboratory, where all tissue banking, biospecimen processing, and immune assays are conducted. The Biostatistics Core (C) and Informatics Core (D) support all projects with data analysis and management, respectively. We will continue to solicit, review, and fund applications for the career development and developmental research programs, which in the prior funding period led to the design of a new full project in this application (Project 3) and the promotion of career development recipients to co-investigators and a project leader.