Abstract
Melanoma is a malignant neoplasm with a high propensity to metastasize, arising from melanocytes and contributing significantly to global morbidity and mortality. Despite the demonstrated efficacy of many immunotherapy approaches, these methods rely on direct destruction of tumor cells with minimal impact on the aggregate of nearby non-tumor cells, the extracellular matrix, and blood vessels that form the tumor microenvironment (TME). The TME is known to be heterogeneous and dynamic, exerting both antitumor and pro-tumor effects depending on the specific features and stage of carcinogenesis. TME has been shown in several studies to promote malignancy, angiogenesis, and metastasis in tumors in general and melanoma in particular. Consequently, a significant number of studies in the field of melanoma therapy have been redirected to investigate the effects of individual TME constituents, their prognostic significance for patients, and the potential of therapeutic intervention to improve overall patient survival. This review highlights novel therapeutic approaches targeting two key resident cell types in the melanoma microenvironment: tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). The review discusses their role in disease progression and summarizes the results of preclinical and clinical trials of targeted therapies against these cell types in the melanoma TME.