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Merkel Cell Carcinoma in the Age of Immunotherapy: Facts and Hopes

Colunga, Aric ; Pulliam, Thomas ; Nghiem, Paul

Clinical cancer research, 2018-05, Vol.24 (9), p.2035-2043 [Periódico revisado por pares]

United States: American Association for Cancer Research Inc

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Título:
Merkel Cell Carcinoma in the Age of Immunotherapy: Facts and Hopes
Autor: Colunga, Aric ; Pulliam, Thomas ; Nghiem, Paul
Assuntos: Animals ; Antibodies, Viral - immunology ; Antibodies, Viral - pharmacology ; Antigens ; Antigens, Viral, Tumor - immunology ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Antitumor activity ; Biomarkers, Tumor ; Carcinoma, Merkel Cell - diagnosis ; Carcinoma, Merkel Cell - etiology ; Carcinoma, Merkel Cell - immunology ; Carcinoma, Merkel Cell - therapy ; Chemotherapy ; Clinical trials ; Combined Modality Therapy ; Cytotoxicity ; Humans ; Immune checkpoint ; Immune response ; Immunogenicity ; Immunomodulation ; Immunotherapy ; Immunotherapy - methods ; Lymphocytes ; Lymphocytes T ; Medical research ; Merkel cell polyomavirus - immunology ; Monoclonal antibodies ; Mutation ; Neoantigens ; Neuroendocrine tumors ; Patients ; PD-1 protein ; PD-L1 protein ; Polyomavirus Infections - complications ; Polyomavirus Infections - immunology ; Polyomavirus Infections - virology ; Programmed Cell Death 1 Receptor - metabolism ; Regulatory agencies ; Skin ; Standard of Care ; Targeted cancer therapy ; Tumor Burden ; Tumor Virus Infections - complications ; Tumor Virus Infections - immunology ; Tumor Virus Infections - virology ; Tumors ; Ultraviolet radiation ; Ultraviolet Rays ; Viruses
É parte de: Clinical cancer research, 2018-05, Vol.24 (9), p.2035-2043
Descrição: Merkel cell carcinoma (MCC) is a rare (∼2,000 U.S. cases/year) but aggressive neuroendocrine tumor of the skin. For advanced MCC, cytotoxic chemotherapy only infrequently (<10% of cases) offers durable clinical responses (>1 year), suggesting a great need for improved therapeutic options. In 2008, the Merkel cell polyomavirus (MCPyV) was discovered and is clonally integrated in approximately 80% of MCC tumors. The remaining 20% of MCC tumors have large numbers of UV-associated mutations. Importantly, both the UV-induced neoantigens in virus-negative tumors and the MCPyV T antigen oncogenes that are required for virus-positive tumor growth are immunogenic. Indeed, antigen-specific T cells detected in patients are frequently dysfunctional/"exhausted," and the inhibitory ligand, PD-L1, is often present in MCC tumors. These findings led to recent clinical trials involving PD-1 pathway blockade in advanced MCC. The combined data from these trials involving three PD-1 pathway blocking agents-avelumab, pembrolizumab, and nivolumab-indicated a high frequency of durable responses in treated patients. Of note, prior treatment with chemotherapy was associated with decreased response rates to PD-1 checkpoint blockade. Over the past year, these striking data led to major changes in advanced MCC therapy, including the first-ever FDA drug approval for this disease. Despite these successes, approximately 50% of patients with MCC do not persistently benefit from PD-1 pathway blockade, underscoring the need for novel strategies to broaden antitumor immune responses in these patients. Here, we highlight recent progress in MCC including the underlying mechanisms of immune evasion and emerging approaches to augment the efficacy of PD-1 pathway blockade. .
Editor: United States: American Association for Cancer Research Inc
Idioma: Inglês

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Merkel Cell Carcinoma in the Age of Immunotherapy: Facts and Hopes

Colunga, Aric ; Pulliam, Thomas ; Nghiem, Paul

United States: American Association for Cancer Research Inc

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