The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 
1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular 
and immune advances; (2) combination therapies; (3) news in immunotherapy; and 
4) tumor microenvironment and biomarkers. Recent advances in tumor biology and 
immunology has led to the development of new targeted and immunotherapeutic 
agents that prolong progression-free survival (PFS) and overall survival (OS) of 
cancer patients. Immunotherapies in particular have emerged as highly successful 
approaches to treat patients with cancer including melanoma, non-small cell lung 
cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's 
disease. Specifically, many clinical successes have been using checkpoint 
receptor blockade, including T cell inhibitory receptors such as cytotoxic 
T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death-1 
(PD-1) and its ligand PD-L1. Despite demonstrated successes, responses to 
immunotherapy interventions occur only in a minority of patients. Attempts are 
being made to improve responses to immunotherapy by developing biomarkers. 
Optimizing biomarkers for immunotherapy could help properly select patients for 
treatment and help to monitor response, progression and resistance that are 
critical challenges for the immuno-oncology (IO) field. Importantly, biomarkers 
could help to design rational combination therapies. In addition, biomarkers may 
help to define mechanism of action of different agents, dose selection and to 
sequence drug combinations. However, biomarkers and assays development to guide 
cancer immunotherapy is highly challenging for several reasons: (i) multiplicity 
of immunotherapy agents with different mechanisms of action including 
immunotherapies that target activating and inhibitory T cell receptors (e.g., 
CTLA-4, PD-1, etc.); adoptive T cell therapies that include tissue infiltrating 
lymphocytes (TILs), chimeric antigen receptors (CARs), and T cell receptor (TCR) 
modified T cells; (ii) tumor heterogeneity including changes in antigenic 
profiles over time and location in individual patient; and (iii) a variety of 
immune-suppressive mechanisms in the tumor microenvironment (TME) including T 
regulatory cells (Treg), myeloid derived suppressor cells (MDSC) and 
immunosuppressive cytokines. In addition, complex interaction of tumor-immune 
system further increases the level of difficulties in the process of biomarkers 
development and their validation for clinical use. Recent clinical trial results 
have highlighted the potential for combination therapies that include 
immunomodulating agents such as anti-PD-1 and anti-CTLA-4. Agents targeting 
other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) 
receptors on T cells and other approaches such as adoptive cell transfer are 
tested for clinical efficacy in melanoma as well. These agents are also being 
tested in combination with targeted therapies to improve upon shorter-term 
responses thus far seen with targeted therapy. Various locoregional 
interventions that demonstrate promising results in treatment of advanced 
melanoma are also integrated with immunotherapy agents and the combinations with 
cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving 
landscape of therapeutic options and are being evaluated to prevent or delay 
resistance and to further improve survival rates for melanoma patients' 
population. This meeting's specific focus was on advances in immunotherapy and 
combination therapy for melanoma. The importance of understanding of melanoma 
genomic background for development of novel therapies and biomarkers for 
clinical application to predict the treatment response was an integral part of 
the meeting. The overall emphasis on biomarkers supports novel concepts toward 
integrating biomarkers into personalized-medicine approach for treatment of 
patients with melanoma across the entire spectrum of disease stage. Translation 
of the knowledge gained from the biology of tumor microenvironment across 
different tumors represents a bridge to impact on prognosis and response to 
therapy in melanoma. We also discussed the requirements for pre-analytical and 
analytical as well as clinical validation process as applied to biomarkers for 
cancer immunotherapy. The concept of the fit-for-purpose marker validation has 
been introduced to address the challenges and strategies for analytical and 
clinical validation design for specific assays.