The significance of tumor microenvironment for immunotherapy in melanoma and non-melanoma skin cancer.

Abstract

Immune checkpoint inhibitors (ICIs), such as anti-PD-1 antibody, have significantly changed the treatment landscape not only for unresectable melanoma but also for non-melanoma skin cancers. In addition, anti-PD-1 antibody administration methods have evolved and are now used in both the neoadjuvant and adjuvant settings. As these treatment strategies have been evaluated, it has become clear that understanding the role of the tumor microenvironment (TME) is critical to the success of anti-PD-1 antibody-based immunotherapy. For example, racial differences in the efficacy of immunotherapy in melanoma are influenced not only by tumor-related factors such as tumor mutational burden and microsatellite instability, but also by components of the TME, including tumor-associated macrophages, cancer-associated fibroblasts, and tumor-infiltrating lymphocytes (TILs), all of which can affect the therapeutic outcome of ICIs. Furthermore, studies conducted during the development of neoadjuvant therapies have shown that tumor-reactive TILs are densely localized within primary tumors and are closely associated with both treatment efficacy and the occurrence of immune-related adverse events. In this review, we discuss the therapeutic efficacy of currently available anti-PD-1 antibody-based immunotherapies for skin cancer and examine the role of the TME in influencing these therapeutic outcomes.