ArticleCancer immunology research2014
Regression of metastatic Merkel cell carcinoma following transfer of polyomavirus-specific T cells and therapies capable of re-inducing HLA class-I.
Article in Cancer immunology research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 97 citations in OpenAlex.
- Immune Checkpoint Inhibitors in Merkel Cell Carcinoma of the Skin: A 2025 Comprehensive Review.Cancers · 2025Review
- Targeting archetypes of viral-driven cancers with immunotherapy: a perspective on immunogenicity within the tumor microenvironment.Frontiers in immunology · 2025Review
- Applications of cell therapy in the treatment of virus-associated cancers.Nature reviews. Clinical oncology · 2024Review
- Merkel Cell Carcinoma: Integrating Epidemiology, Immunology, and Therapeutic Updates.American journal of clinical dermatology · 2024Review
- Polyomavirus-positive Merkel cell carcinoma: the beginning of the beginning.The Journal of clinical investigation · 2024Article
- T antigen-specific CD8+ T cells associate with PD-1 blockade response in virus-positive Merkel cell carcinoma.The Journal of clinical investigation · 2024Article
- Possible association between polyomaviruses and gastrointestinal complications: a narrative review.Gastroenterology and hepatology from bed to bench · 2024Review
- Preoperative chemoradiotherapy induces multiple pathways related to anti-tumour immunity in rectal cancer.British journal of cancer · 2023Article
- The common HLA class I-restricted tumor-infiltrating T cell response in HPV16-induced cancer.Cancer immunology, immunotherapy : CII · 2023Article
- Naive T cells inhibit the outgrowth of intractable antigen-activated memory T cells: implications for T-cell immunotherapy.Journal for immunotherapy of cancer · 2023Article
- Article
- Engineered T cell therapy for viral and non-viral epithelial cancers.Cancer cell · 2023Review
- Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor-Based Cellular Therapy.Annual review of cancer biology · 2023Article
- Deciphering the roles of myeloid derived suppressor cells in viral oncogenesis.Frontiers in immunology · 2023Review
- Pathogen-specific T Cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond.HemaSphere · 2023Review
- Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of nonmelanoma skin cancer.Journal for immunotherapy of cancer · 2022Article
- Nationwide multidisciplinary consensus on the clinical management of Merkel cell carcinoma: a Delphi panel.Journal for immunotherapy of cancer · 2022Article
- Development and therapeutic manipulation of the head and neck cancer tumor environment to improve clinical outcomes.Frontiers in oral health · 2022Review
- Adoptive Cell Therapy in Pediatric and Young Adult Solid Tumors: Current Status and Future Directions.Frontiers in immunology · 2022Review
- Merkel cell carcinoma.Skin health and disease · 2021Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Merkel cell carcinoma (MCC) is an aggressive skin cancer that typically requires the persistent expression of Merkel cell polyomavirus (MCPyV) oncoproteins that can serve as ideal immunotherapeutic targets. Several immune evasion mechanisms are active in MCC including down-regulation of HLA class-I expression on tumor cells and dysfunctional endogenous MCPyV-specific CD8 T cell responses. To overcome these obstacles, we combined local and systemic immune therapies in a 67-year-old man, who developed metastatic MCPyV-expressing MCC. Intralesional IFNβ-1b or targeted single-dose radiation was administered as a pre-conditioning strategy to reverse the down-regulation of HLA-I expression noted in his tumors and to facilitate the subsequent recognition of tumor cells by T cells. This was followed by the adoptive transfer of ex vivo expanded polyclonal, polyomavirus-specific T cells as a source of reactive antitumor immunity. The combined regimen was well-tolerated and led to persistent up-regulation of HLA-I expression in the tumor and a durable complete response in two of three metastatic lesions. Relative to historical controls, the patient experienced a prolonged period without development of additional distant metastases (535 days compared to historic median of 200 days, 95% confidence interval = 154-260 days). The transferred CD8(+) T cells preferentially accumulated in the tumor tissue, remained detectable and functional for >200 days, persisted with an effector phenotype, and exhibited evidence of recent in vivo activation and proliferation. The combination of local and systemic immune stimulatory therapies was well-tolerated and may be a promising approach to overcome immune evasion in virus-driven cancers.
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Registered trials
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