Biomarkers predictive of response to immunotherapy in melanoma

There is a medical need to identify biomarkers in melanoma patients treated with immunotherapy because firstly diverse immunotherapy options (monotherapy, dual therapy, etc.) could be selected for a given line of treatment and secondly one does not know which patients would benefit from immunotherapy and when to stop treatment or offer adjuvant therapy. The amplification of a pre-existing T, or even B, lymphocyte response against tumor cells seems to be a prerequisite for the efficacy of immune checkpoint inhibitors (ICIs), in particular those blocking the PD-1/PD-L1 axis. Different biomarkers related to this host response have been reported (infiltration by different subpopulations of CD8+ T lymphocytes, mutational load and neoepitopes, IFNy signature, expression of PD-L1 and in particular its interaction with PD-1, presence of tertiary lymphoid structures). Nevertheless, limitations in the use of these biomarkers have been reported such as the presence of tumor heterogeneity and the difficulty to distinguish a biomarker related to prognosis and disease severity independently of treatment. These considerations have motivated the development of biomarkers that take into account this heterogeneity, as their values reflect the entirety of the disease such as circulating tumor DNA, blood biomarkers, metabolic imaging, or immuno-PET. While many biomarkers have been investigated in the context of melanoma immunotherapy, a minority has been approved by regulatory authorities. The main pitfalls are the lack of prospective validation on large cohorts, the reproducibility and feasibility of using these biomarkers in routine clinical practice and the arrival of new treatments that challenge their relevance.& COPY; 2023 l'Academie nationale de medecine. Published by Elsevier Masson SAS. All rights reserved.