Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal.,Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes.,If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level.,Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies.,In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study.,The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered.,The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation.,An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility.,The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association.,As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges.
Adoptive Cell Transfer (ACT) of Tumor-Infiltrating Lymphocytes (TIL) in combination with lymphodepletion has proven to be an effective treatment for metastatic melanoma patients, with an objective response rate in 50%-70% of the patients.,It is based on the ex vivo expansion and activation of tumor-specific T lymphocytes extracted from the tumor and their administration back to the patient.,Various TIL-ACT trials, which differ in their TIL generation procedures and patient preconditioning, have been reported.,In the latest clinical studies, genetically engineered peripheral T cells were utilized instead of TIL.,Further improvement of adoptive T cell transfer depends on new investigations which seek higher TIL quality, increased durable response rates, and aim to treat more patients.,Simplifying this therapy may encourage cancer centers worldwide to adopt this promising technology.,This paper focuses on the latest progress regarding adoptive T cell transfer, comparing the currently available protocols and discussing their advantages, disadvantages, and implication in the future.