Molecular and Immune Biomarkers for Cutaneous Melanoma: Current Status and Future Prospects

Abstract

Advances in the genomic, molecular and immunological make-up of melanoma allowed the development of novel targeted therapy and of immunotherapy, leading to changes in the paradigm of therapeutic interventions and improvement of patients’ overall survival. Nevertheless, the mechanisms regulating either the responsiveness or the resistance of melanoma patients to therapies are still mostly unknown. The development of either the combinations or of the sequential treatment of different agents has been investigated but without a strongly molecularly motivated rationale. The need for robust biomarkers to predict patients’ responsiveness to defined therapies and for their stratification is still unmet. Progress in immunological assays and genomic techniques as long as improvement in designing and performing studies monitoring the expression of these markers along with the evolution of the disease allowed to identify candidate biomarkers. However, none of them achieved a definitive role in predicting patients’ clinical outcomes. Along this line, the cross-talk of melanoma cells with tumor microenvironment plays an important role in the evolution of the disease and needs to be considered in light of the role of predictive biomarkers. The overview of the relationship between the molecular basis of melanoma and targeted therapies is provided in this review, highlighting the benefit for clinical responses and the limitations. Moreover, the role of different candidate biomarkers is described together with the technical approaches for their identification. The provided evidence shows that progress has been achieved in understanding the molecular basis of melanoma and in designing advanced therapeutic strategies. Nevertheless, the molecular determinants of melanoma and their role as biomarkers predicting patients’ responsiveness to therapies warrant further investigation with the vision of developing more effective precision medicine.

The Prediction Potential of the Pretreatment Lung Immune Prognostic Index for the Therapeutic Outcomes of Immune Checkpoint Inhibitors in Patients With Solid Cancer: A Systematic Review and Meta-Analysis

“…Until now, there is still no biomarker for some cancers to predict the response or resistance to immunotherapy ( 6 ). Robust biomarkers are needed to predict patient responsiveness to immunotherapy and for their stratification ( 35 ). Our meta-analysis provides new evidence supporting that LIPI scores are used as prognostic indicators for cancer patients receiving ICIs or chemotherapy.…”

Association of TRF2 expression and myeloid-derived suppressor cells infiltration with clinical outcome of patients with cutaneous melanoma

“… 33 , 34 Thus, despite active research and development for having robust prognostic or predictive biomarkers for responsiveness of ICIs in melanoma in routine clinical practice, there is an urgent need for robust and easy to use biomarkers in daily practice to guide the clinical decision-making. 35 , 36 …”

Role of Hypoxia and the Adenosine System in Immune Evasion and Prognosis of Patients with Brain Metastases of Melanoma: A Multiplex Whole Slide Immunofluorescence Study

“…CTL infiltration in the tumor microenvironment alone, however, does not provide a comprehensive assessment of antitumoral immune activity [ 44 ]. The immune infiltrate rather represents a multifaceted component of the TME, which is determined by the interaction of tumor related factors, such as the tumor biology, and host factors, i.e., the ability of the patient’s immune system to respond effectively to tumors [ 44 ].…”

“…CTL infiltration in the tumor microenvironment alone, however, does not provide a comprehensive assessment of antitumoral immune activity [ 44 ]. The immune infiltrate rather represents a multifaceted component of the TME, which is determined by the interaction of tumor related factors, such as the tumor biology, and host factors, i.e., the ability of the patient’s immune system to respond effectively to tumors [ 44 ]. In the future, it will be possible to simultaneously visualize additional markers of immune cell activation and exhaustion [ 45 , 46 ] in approaches using higher multiplexing techniques, allowing for a more differentiated analysis (CTLA-4, LAG-3, CD62L, CCR7, or PD-1) [ 47 ].…”