Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 1st–3rd, 2022—Naples, Italy)

Abstract

Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). Combinations of these checkpoint therapies with other agents are now being explored to improve outcomes and enhance benefit-risk profiles of treatment. Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have several potential target oncogenes for molecularly targeted therapy, such as tyrosine kinase inhibitors. Unfortunately, many patients still progress and acquire resistance to immunotherapy and molecularly targeted therapies. To bypass resistance, combination treatment with immunotherapies and single or multiple TKIs have been shown to improve prognosis compared to monotherapy. The number of new combinations treatment under development for melanoma provides options for the number of patients to achieve a therapeutic benefit. Many diagnostic and prognostic assays have begun to show clinical applicability providing additional tools to optimize and individualize treatments. However, the question on the optimal algorithm of first- and later-line therapies and the search for biomarkers to guide these decisions are still under investigation. This year, the Melanoma Bridge Congress (Dec 1st–3rd, 2022, Naples, Italy) addressed the latest advances in melanoma research, focusing on themes of paramount importance for melanoma prevention, diagnosis and treatment. This included sessions dedicated to systems biology on immunotherapy, immunogenicity and gene expression profiling, biomarkers, and combination treatment strategies.

Galectin-3 and cancer immunotherapy: a glycobiological rationale to overcome tumor immune escape

“…The increased number of functional CD8 + T-cells detected in the TME of Galectin-3 KO mice and the expansion of plasmacytoid dendritic cells, which are potent activators of CD8 + cells, compared to Galectin-3 WT-mice, reinforce the evidence of the existing cross-talk between LAG-3 (immune checkpoint) and Galectin-3 [ 10 ]. Very recently, treatments of BRAF-mutant melanomas with combination therapies including anti-LAG-3 targeting, showed excellent results [ 11 ]. The mechanism by which LAG-3 mediates CD8 + T-cell activity is not fully understood.…”

“…The intriguing hypothesis that a Galectin-3 rich -TME could be responsible, at least in part, of tumor immune escape, deserves further investigation [ 10 , 11 ].…”