Current status of skin cancers with a focus on immunology and immunotherapy

Abstract

Skin cancer is one of the most widespread cancers, with a significant global health effect. UV-induced DNA damage in skin cells triggers them to grow and proliferate out of control, resulting in cancer development. Two common types of skin cancer include melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC). Melanoma is the most lethal form of skin cancer, and NMSC includes basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and other forms. The incidence of skin cancer is increasing in part owing to a demographic shift toward an aging population, which is more prone to NMSC, imposing a considerable financial strain on public health services. The introduction of immunostimulatory approaches for cancer cell eradication has led to significant improvements in skin cancer treatment. Over the last three decades, monoclonal antibodies have been used as powerful human therapeutics besides scientific tools, and along with the development of monoclonal antibody production and design procedures from chimeric to humanized and then fully human monoclonal antibodies more than 6 monoclonal antibodies have been approved by the food and drug administration (FDA) and have been successful in skin cancer treatment. In this review, we will discuss the epidemiology, immunology, and therapeutic approaches of different types of skin cancer.

Keywords: Melanoma; Monoclonal antibody; Non-melanoma skin cancer; Skin cancer.

Fig. 1

Melanocyte’s function in skin immunity. Melanocytes produce melanin which protects DNA from UV radiation and melanocytes enhance expression of MHC-II and produce cytokines and chemokines, develop pathogen phagocytosis and control innate and adaptive local immune responses

Fig. 2

Keratinocyte’s function in skin immunity. Keratinocytes are important in maintaining the mechanical and functional barrier of epidermis and produce cytokines besides express MHC I and II and act as APCs and induce T cell responses by producing the cytokines

Fig. 3

Relation between B and T cells in skin. B cells can also play the role of APCs for naive T cells and activated CD4⁺ T cells promote naive B cells to be activated

Fig. 4

Immune check point inhibitors: Recent evidence confirmed the significant clinical benefit from using immune check point inhibitors,this figure demonstrates the mechanism underlying its beneficial effect

Fig. 5

Ant- PD-1 mechanism of action.Programmed cell death protein 1 (PD-1) is an immune checkpoint and causes apoptosis of antigen-specific T-cells in lymph nodes and reduces apoptosis in regulatory T cells. PD-1 inhibitors block PD-1 and activate the immune system to attack tumors