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

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...

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Main Author: Taku Fujimura
Format: Article
Language:English
Published: Taylor & Francis Group 2025-08-01
Series:Immunological Medicine
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Online Access:https://www.tandfonline.com/doi/10.1080/25785826.2025.2550795
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author Taku Fujimura
author_facet Taku Fujimura
author_sort Taku Fujimura
collection DOAJ
description 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.
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spelling doaj-art-dae7366db8cd4a53a8b59c07b66d1f072025-08-25T11:03:11ZengTaylor & Francis GroupImmunological Medicine2578-58262025-08-0111110.1080/25785826.2025.2550795The significance of tumor microenvironment for immunotherapy in melanoma and non-melanoma skin cancerTaku Fujimura0Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, JapanImmune 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.https://www.tandfonline.com/doi/10.1080/25785826.2025.2550795Immune checkpoint inhibitorsanti-PD-1 antibodycombination therapytolerancetumor microenvironment
spellingShingle Taku Fujimura
The significance of tumor microenvironment for immunotherapy in melanoma and non-melanoma skin cancer
Immunological Medicine
Immune checkpoint inhibitors
anti-PD-1 antibody
combination therapy
tolerance
tumor microenvironment
title The significance of tumor microenvironment for immunotherapy in melanoma and non-melanoma skin cancer
title_full The significance of tumor microenvironment for immunotherapy in melanoma and non-melanoma skin cancer
title_fullStr The significance of tumor microenvironment for immunotherapy in melanoma and non-melanoma skin cancer
title_full_unstemmed The significance of tumor microenvironment for immunotherapy in melanoma and non-melanoma skin cancer
title_short The significance of tumor microenvironment for immunotherapy in melanoma and non-melanoma skin cancer
title_sort significance of tumor microenvironment for immunotherapy in melanoma and non melanoma skin cancer
topic Immune checkpoint inhibitors
anti-PD-1 antibody
combination therapy
tolerance
tumor microenvironment
url https://www.tandfonline.com/doi/10.1080/25785826.2025.2550795
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