Oncolytic viral therapy for nonmelanoma skin cancer and cutaneous lymphoma - A systematic review

Abstract

The rising incidence and consequent health care burden of nonmelanoma skin cancers, including cutaneous lymphomas, are a growing cause for concern. Oncolytic viruses (OVs) are emerging immunotherapies with limited literature on their use. We conducted a systematic review to evaluate their role in nonmelanoma skin cancer and cutaneous lymphoma treatment (CRD42024526854). We identified 11 published studies involving a total of 20 patients (squamous cell carcinoma n = 3, Merkel cell carcinoma n = 7, cutaneous T cell lymphoma n = 9, basal cell carcinoma n = 1). OVs used include Talimogene laherparepvec (73%, n = 8), measles virus (9%, n = 1), vesicular stomatitis virus (9%, n = 1), and adenovirus (9%, n = 1). Complete response occurred in 67% (n = 2) of squamous cell carcinoma cases, 85% (n = 6) of Merkel cell carcinoma cases, and 11% (n = 1) of cutaneous T cell lymphoma cases. The most common adverse event was fever or flu-like symptoms (n = 5, 25%). Fourteen unpublished clinical trials investigating regimes such as OV monotherapy (43%, n = 6), combination therapy with existing immunotherapy (21%, n = 3), and comparing OV combination versus monotherapy (29%, n = 4) or versus immune checkpoint inhibitor alone (7%, n = 1). Overall, heterogeneity of existing studies significantly limits generalizability of results. Further research is needed to reveal the potential role of OVs in the future of nonmelanoma skin cancer and cutaneous lymphoma treatment.

Keywords: epidemiology; nonmelanoma skin cancer; oncolytic virus; virotherapy.

Fig 1

A, Summary of systematic review performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. B, Mechanisms of Action of Oncolytic Viruses. (A) Remodeling of tumor microenvironment: Viral particles released by oncolytic viruses alter cytokines and immune cells within the tumor microenvironment to stimulate a local immune response. This results in lysis of tumor cells, which at the same time releases neo-antigens that can subsequently trigger a de novo immune response at distant sites. (B) Direct tumor lysis: Direct infection and replication within cancer cells which eventually results in lysis of infected cells. (C) Induction of systemic antitumor immune response: Release of viral pathogen-associated molecular patterns, danger-associated molecular pattern signals, and tumor associated antigens stimulate adaptive immune cells, which then travel to sites of tumor growth and mediate antitumor immunity.