Immunotherapy in Basal Cell Carcinoma

Abstract

Basal cell carcinoma (BCC) is the most frequent of all cancers, with an increasing incidence. The first line therapy is surgical excision, but topical therapies can be used in low-risk superficial BCCs, while the more advanced, unresectable, or metastatic BCCs benefit from systemic therapies with hedgehog inhibitors and immunotherapy. The purpose of this review is to highlight local and systemic immunotherapies and their efficacy in the management of BCCs. Local therapies can be considered in superficial and low-risk nodular BCCs, with imiquimod frequently used for its antitumor and immunoregulatory properties. Imiquimod alone demonstrated higher histological clearance rates, but patients treated with imiquimod experienced more adverse events than ones treated with other therapies. Imiquimod can be used as an adjuvant before Mohs micrographic surgery and can also be combined with other local therapies, like curettage, electrodesiccation, cryosurgery, and photodynamic therapy, with some treatment methods yielding results comparable with the surgery. Interferons and Interleukin-2 were evaluated in a small number of studies with different results. Systemic immunotherapies with programmed death-ligand 1 (PD-L1) inhibitors showed inconsistent results in patients with advanced BCCs, being effective in some patients that progressed on or were intolerant to hedgehog pathway inhibitors (HHI).

Keywords: basal cell carcinoma; check point inhibitors; imiquimod; immunotherapy.

Figure 1

The immune microenvironment of basal cell carcinoma (TILS—tumor infiltrating lymphocytes; IL2—interleukin-2; IL17—interleukin-17; IL22—interleukin-22; IL4—interleukin-4; IL10—interleukin-10; IL5—interleukin-5; IL13—interleukin-13; IL10—interleukin-10; IL1β—interleukin 1β; IFN γ—Interferon gamma; TNF β—Tumor Necrosis Factor β; Treg—Regulatory T cells; Th1 immune response—Type 1 T Helper immune response; ECM—extracellular matrix; Th2—Type 2 T Helper).