Epigenetic Modification of PD-1/PD-L1-Mediated Cancer Immunotherapy against Melanoma

Abstract

Malignant melanoma is one of the representative skin cancers with unfavorable clinical behavior. Immunotherapy is currently used for the treatment, and it dramatically improves clinical outcomes in patients with advanced malignant melanoma. On the other hand, not all these patients can obtain therapeutic efficacy. To overcome this limitation of current immunotherapy, epigenetic modification is a highlighted issue for clinicians. Epigenetic modification is involved in various physiological and pathological conditions in the skin. Recent studies identified that skin cancer, especially malignant melanoma, has advantages in tumor development, indicating that epigenetic manipulation for regulation of gene expression in the tumor can be expected to result in additional therapeutic efficacy during immunotherapy. In this review, we focus on the detailed molecular mechanism of epigenetic modification in immunotherapy, especially anti-PD-1/PD-L1 antibody treatment for malignant melanoma.

Keywords: anti-PD-L1 antibody; anti-PD1 antibody; epigenetics; malignant melanoma.

Figure 1

Epigenetic histone modification (A) Histone modification. DNA binds to histone for gene repression, while the weak connection of DNA and histone activates gene transcription. (B) Histone binds to DNA via voltage connection, which is canceled by HAT-mediated histone acetylation. HDAC cancels the histone acetylation, leading to gene repression.