Insights into the Molecular Mechanisms Behind Intralesional Immunotherapies for Advanced Melanoma

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.

Pituitary Adenylate Cyclase Activating Polypeptide Has Inhibitory Effects on Melanoma Cell Proliferation and Migration In Vitro

“…Invasiveness is a key neoplastic feature, offering the ability of malignant cells to penetrate healthy tissues and to establish new local tumour cell clusters. Several mutations have been identified in melanoma that affect signalling pathways involved in cellular motility leading eventually to invasion and metastasis formation ( 65 ). Therefore, the next step was to examine the effects of extrinsic PACAP on fibronectin-guided migration and invasion of melanoma cells.…”

Case Report: Combined Intra-Lesional IL-2 and Topical Imiquimod Safely and Effectively Clears Multi-Focal, High Grade Cutaneous Squamous Cell Cancer in a Combined Liver and Kidney Transplant Patient

“…Furthermore, by delivering an increased concentration of the active agent at the site of action, increased rates of efficacy are observed (84,85). To date, only a handful of intra-lesional agents have been used for treatment of cSCC, although this method of delivery has been extensively studied in melanoma wherein systemic adverse events are minimized and the local immune response is maximized (86).…”

“…Interestingly, other potent T cell activating immunotherapies such as IL-2, have not yet been studied in the context of cSCC, to our knowledge. This is despite its extensive investigation as an intra-lesional agent in melanoma (86,(103)(104)(105) and HNSCC (106)(107)(108)(109), where it mediates a shift to CD8+ T cell-mediated tumor clearance. The excellent response demonstrated by this case warrants further investigation into the possible role intralesional IL-2 may have in the treatment of cSCC.…”

Intralesional Avirulent Bacillus Calmette-Guérin Injection as a Promising Method for the Treatment of Tuberculosis Verrucosa Cutis

“…Although the roots of this concept (using the patient's own immune system to fight an active disease) can be traced back to the works of Dr. William Coley in the late 19th century, it is only recently that there has been a widespread emerging interest in it in dermatology [ 9 ]. The current main focus of dermatological immunotherapy is the treatment of melanoma, multiple warts, and alopecia areata [ 10 , 11 , 12 ]. In this paper, we report our clinical observation on the healing process of a patient with recalcitrant TBVC after intralesional injection of avirulent Bacillus Calmette-Guérin (BCG).…”