The term “non-melanoma skin cancer” (NMSC) includes a wide range of cutaneous tumors, some of which are very common, including cutaneous squamous cell carcinoma (CSCC) and basal cell carcinoma (BCC), and others which are very rare, including Merkel cell carcinoma (MCC) and dermatofibrosarcoma protuberans. NMSC represents the most frequently diagnosed human cancer and its incidence is constantly growing. Although the majority of NMSC are treated with conventional surgery and/or radiotherapy, a small percentage of patients progress to locally advanced or metastatic disease, mainly due to patient negligence, comorbidities, or immunosuppression. In these circumstances, systemic treatment may be indicated. Until recently, effective therapy remained an area of significant unmet clinical need. Improved understanding of molecular and immune pathogenesis has been critical to driving and developing new therapeutic advances, particularly towards immunotherapy. Thanks to their high mutational tumor burden and the consequent high neoantigen burden, all NMSCs are theoretically suitable for immunotherapy; albeit the robustness of their immunological response is quite different. Moreover, in the face of a powerful immune reaction, many patients progress or do not respond to modern immunotherapy due to resistance or immunoescape mechanisms.
Advanced basal cell carcinoma (BCC) has no effective treatment option beyond the Hedgehog inhibitors. BCC harbors a high genetic mutational and neoantigen burden, which is reported to be among the highest in any human cancer. Moreover, high PD-L1 expression was observed in the BCC micro-environment in close geographic association to PD-1+ tumor-infiltrating lymphocytes. Finally, during Hedgehog inhibitor treatment, an up-regulation of MHC I expression and an influx of CD4, HLA-DR-class II, and CD8 cells with invasion into the tumor cell nests were reported. Cases of response to anti-PD1 antibodies have been recently reported in patients with Hedgehog inhibitor-resistance.
Cutaneous squamous cell carcinoma (CSCC) is often associated with chronic exposure to ultraviolet radiation that causes gene mutations and neoantigens appearance. Before the era of immunotherapy, no other medical therapy had proven to significantly change the clinical history of these patients. Recent studies with immunological checkpoint inhibitors have demonstrated an objective response of about 50%, with approximately 10% of complete responses, and approximately 80% of one-year survival.
Merkel-cell carcinoma (MCC) is a rare and highly aggressive form of skin cancer, particularly common in elderly people. Several factors are involved in the pathophysiology of MCC including polyomavirus, ultraviolet radiation exposure, and weakened immune function. In the advanced disease, systemic chemotherapy was used in the past with disappointing results. Checkpoint inhibitors anti–PD1/anti-PDL1 have recently been investigated for first and second-line treatment, reporting positive outcomes. Data in adjuvant and neoadjuvant settings are also very promising.
The aim of this Research Topic is to provide clinicians an overview of innovative systemic treatments for NMSC, mainly oriented towards immunotherapy. Adjuvant and neoadjuvant settings, as well as future therapeutic directions, will also be highlighted. We’d like to also encourage innovative therapeutic approaches through integrated basic research strategies.
We welcome Reviews or Original Research manuscripts that explore, but are not limited to, the following themes:
? The rationale for immunotherapy in non-melanoma skin cancers
? Immunotherapy in basal cell carcinoma, cutaneous squamous cell carcinoma and/or Merkel-cell carcinoma: current therapeutic options and future directions
? Adjuvant and neoadjuvant approaches in non-melanoma skin cancer
The term “non-melanoma skin cancer” (NMSC) includes a wide range of cutaneous tumors, some of which are very common, including cutaneous squamous cell carcinoma (CSCC) and basal cell carcinoma (BCC), and others which are very rare, including Merkel cell carcinoma (MCC) and dermatofibrosarcoma protuberans. NMSC represents the most frequently diagnosed human cancer and its incidence is constantly growing. Although the majority of NMSC are treated with conventional surgery and/or radiotherapy, a small percentage of patients progress to locally advanced or metastatic disease, mainly due to patient negligence, comorbidities, or immunosuppression. In these circumstances, systemic treatment may be indicated. Until recently, effective therapy remained an area of significant unmet clinical need. Improved understanding of molecular and immune pathogenesis has been critical to driving and developing new therapeutic advances, particularly towards immunotherapy. Thanks to their high mutational tumor burden and the consequent high neoantigen burden, all NMSCs are theoretically suitable for immunotherapy; albeit the robustness of their immunological response is quite different. Moreover, in the face of a powerful immune reaction, many patients progress or do not respond to modern immunotherapy due to resistance or immunoescape mechanisms.
Advanced basal cell carcinoma (BCC) has no effective treatment option beyond the Hedgehog inhibitors. BCC harbors a high genetic mutational and neoantigen burden, which is reported to be among the highest in any human cancer. Moreover, high PD-L1 expression was observed in the BCC micro-environment in close geographic association to PD-1+ tumor-infiltrating lymphocytes. Finally, during Hedgehog inhibitor treatment, an up-regulation of MHC I expression and an influx of CD4, HLA-DR-class II, and CD8 cells with invasion into the tumor cell nests were reported. Cases of response to anti-PD1 antibodies have been recently reported in patients with Hedgehog inhibitor-resistance.
Cutaneous squamous cell carcinoma (CSCC) is often associated with chronic exposure to ultraviolet radiation that causes gene mutations and neoantigens appearance. Before the era of immunotherapy, no other medical therapy had proven to significantly change the clinical history of these patients. Recent studies with immunological checkpoint inhibitors have demonstrated an objective response of about 50%, with approximately 10% of complete responses, and approximately 80% of one-year survival.
Merkel-cell carcinoma (MCC) is a rare and highly aggressive form of skin cancer, particularly common in elderly people. Several factors are involved in the pathophysiology of MCC including polyomavirus, ultraviolet radiation exposure, and weakened immune function. In the advanced disease, systemic chemotherapy was used in the past with disappointing results. Checkpoint inhibitors anti–PD1/anti-PDL1 have recently been investigated for first and second-line treatment, reporting positive outcomes. Data in adjuvant and neoadjuvant settings are also very promising.
The aim of this Research Topic is to provide clinicians an overview of innovative systemic treatments for NMSC, mainly oriented towards immunotherapy. Adjuvant and neoadjuvant settings, as well as future therapeutic directions, will also be highlighted. We’d like to also encourage innovative therapeutic approaches through integrated basic research strategies.
We welcome Reviews or Original Research manuscripts that explore, but are not limited to, the following themes:
? The rationale for immunotherapy in non-melanoma skin cancers
? Immunotherapy in basal cell carcinoma, cutaneous squamous cell carcinoma and/or Merkel-cell carcinoma: current therapeutic options and future directions
? Adjuvant and neoadjuvant approaches in non-melanoma skin cancer
