Abstract
The incidence of cutaneous melanoma, a highly malignant skin cancer, is increasing yearly. While surgical removal of the tumor is the mainstay of treatment for patients with locally confined disease, those with metastases face uncertainty when it comes to their treatment. As melanoma is a relatively immunogenic cancer, current guidelines suggest using immunotherapies that can rewire the host immune response to target melanoma tumor cells. Intralesional therapy, where immunomodulatory agents are injected directly into the tumor, are an emerging aspect of treatment for in-transit melanoma because of their ability to mitigate severe off-target immune-related adverse events. However, their immunomodulatory mechanisms are poorly understood. In this review, we will summarize and discuss the different intralesional therapies for metastatic melanoma with respect to their clinical outcomes and immune molecular mechanisms.
Highlights
Cutaneous melanoma is one of the most common forms of cancer today, ranking fifth most common in men and seventh most common in women [1]
Intralesional IL2 likely potentiates the Th1-promoting ability of toll-like receptor 7 (TLR7) activation, which is supported by data revealing that the peripheral CD4+ /CD8+ T cell ratio following treatment with imiquimod and intralesional IL2 is significantly increased in peripheral blood mononuclear cell samples (PBMC) of melanoma patients [56]
Akin to the findings reported with intralesional IL2 and imiquimod alone [56], the peripheral CD4+ /CD8+ T cell ratio was significantly increased, with a specific expansion of both activated T lymphocytes and memory T cell populations [57]
Summary
Cutaneous melanoma is one of the most common forms of cancer today, ranking fifth most common in men and seventh most common in women [1]. While most patients (up to 84%) present with such localized disease, a minority of patients, approximately between 9% and 4%, present with regional or distant metastatic disease (stage III+ disease), respectively [9] Prognosis for these patients is generally poor, as their tumors are often disseminated and unresectable; and unlike other solid tumors, advanced melanoma typically responds poorly to traditional chemotherapy [8]. For those patients with stage III in-transit disease or greater, current guidelines recommend enrolment in a clinical trial or Cancers 2020, 12, 1321; doi:10.3390/cancers12051321 www.mdpi.com/journal/cancers. This review will examine all of the established intralesional therapies used for treatment of advanced melanoma, with a specific focus on the immunological and biochemical mechanisms behind them, and how those affect treatment outcomes
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