Abstract
There are various melanoma treatment strategies that are based on immunological responses, among which immune checkpoint inhibitors (ICI) are relatively novel form. Nowadays, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) antibodies represent a standard treatment for metastatic melanoma. Although there are remarkable curative effects in responders to ICI therapy, up to 70% of melanoma patients show resistance to this treatment. This low response rate is caused by innate as well as acquired resistance, and some aspects of treatment resistance are still unknown. Growing evidence shows that gut microbiota and bacterial metabolites, such as short-chain fatty acids (SCFAs), affect the efficacy of immunotherapy. Various bacterial species have been indicated as potential biomarkers of anti-PD-1 or anti-CTLA-4 therapy efficacy in melanoma, next to biomarkers related to molecular and genetic tumor characteristics or the host immunological response, which are detected in patients’ blood. Here, we review the current status of biomarkers of response to ICI melanoma therapies, their pre-treatment predictive values, and their utility as on-treatment monitoring tools in order to select a relevant personalized therapy on the basis of probability of the best clinical outcome.
Highlights
Melanoma is a skin cancer that arises from the transformed melanocytes
Yamazaki et al [74] reported that higher serum pre-treatment levels of IFN-γ, interleukin 6 (IL-6), and IL-10 were associated with tumor response to nivolumab in melanoma patients and that decreased levels of these cytokines were observed in non-responders
Elevated pre-treatment frequencies of mo-Myeloid-derived suppressor cells (MDSCs) is a marker of a lower response, higher rates of progression, and shorter survival in melanoma patients receiving nivolumab who formerly progressed after ipilimumab therapy [116]
Summary
Melanoma is a skin cancer that arises from the transformed melanocytes. Among skin cancers, malignant melanoma has the highest morbidity rate [1]. Nivolumab and pembrolizumab are anti-PD-1 antibodies that were approved by the FDA for the treatment of advanced melanoma in 2014 and 2015, respectively They bind to the PD-1 receptor on the T-cell surface and block its interaction with PD-L1 and PD-L2, preventing immune suppression stimulated by cancer cells [1]. The increasing number of therapeutic approaches for melanoma patients leads to a need for activity of the immune system and induce inflammation, which can be responsible for developing establishing predictive biomarkers to select a relevant personalized therapy, on the basis of probability immune-related adverse events (irAEs). Pre-treatment melanoma patients from three different perspectives: (i) that related to molecular and genetic tumor predictive biomarkers would be helpful in deciding on the type of therapy. We provide a review of the recent literature on several potential biomarkers of response to ICI therapies related to the tumor characteristics and oncogenic adaptive immune resistance mechanisms
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