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Circulating cancer-specific CD8 T cell frequency is associated with response to PD-1 blockade in Merkel cell carcinoma.
Pulliam, Thomas; Jani, Saumya; Jing, Lichen; Ryu, Heeju; Jojic, Ana; Shasha, Carolyn; Zhang, Jiajia; Kulikauskas, Rima; Church, Candice; Garnett-Benson, Charlie; Gooley, Ted; Chapuis, Aude; Paulson, Kelly; Smith, Kellie N; Pardoll, Drew M; Newell, Evan W; Koelle, David M; Topalian, Suzanne L; Nghiem, Paul.
Afiliación
  • Pulliam T; Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98109, USA.
  • Jani S; Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98109, USA.
  • Jing L; Department of Medicine, University of Washington, Seattle, WA 98109, USA.
  • Ryu H; Vaccine and Infectious Disease Department, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Jojic A; Vaccine and Infectious Disease Department, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Shasha C; Vaccine and Infectious Disease Department, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Zhang J; Department of Oncology, Johns Hopkins University, Baltimore, MD 21827, USA; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21287, USA.
  • Kulikauskas R; Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98109, USA.
  • Church C; Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98109, USA.
  • Garnett-Benson C; Bristol Myers Squibb, Princeton, NJ 08540, USA.
  • Gooley T; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Chapuis A; Department of Medicine, University of Washington, Seattle, WA 98109, USA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Paulson K; Paul G. Allen Research Center, Providence-Swedish Cancer Institute, Seattle, WA 98104, USA; Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA.
  • Smith KN; Department of Oncology, Johns Hopkins University, Baltimore, MD 21827, USA; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21287, USA.
  • Pardoll DM; Department of Oncology, Johns Hopkins University, Baltimore, MD 21827, USA; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21287, USA.
  • Newell EW; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98109, USA; Vaccine and Infectious Disease Department, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Koelle DM; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA; Vaccine and Infectious Disease Department, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Global Health,
  • Topalian SL; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.
  • Nghiem P; Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98109, USA. Electronic address: pnghiem@uw.edu.
Cell Rep Med ; 5(2): 101412, 2024 Feb 20.
Article en En | MEDLINE | ID: mdl-38340723
ABSTRACT
Understanding cancer immunobiology has been hampered by difficulty identifying cancer-specific T cells. Merkel cell polyomavirus (MCPyV) causes most Merkel cell carcinomas (MCCs). All patients with virus-driven MCC express MCPyV oncoproteins, facilitating identification of virus (cancer)-specific T cells. We studied MCPyV-specific T cells from 27 patients with MCC using MCPyV peptide-HLA-I multimers, 26-color flow cytometry, single-cell transcriptomics, and T cell receptor (TCR) sequencing. In a prospective clinical trial, higher circulating MCPyV-specific CD8 T cell frequency before anti-PD-1 treatment was strongly associated with 2-year recurrence-free survival (75% if detectable, 0% if undetectable, p = 0.0018; ClinicalTrial.gov NCT02488759). Intratumorally, such T cells were typically present, but their frequency did not significantly associate with response. Circulating MCPyV-specific CD8 T cells had increased stem/memory and decreased exhaustion signatures relative to their intratumoral counterparts. These results suggest that cancer-specific CD8 T cells in the blood may play a role in anti-PD-1 responses. Thus, strategies that augment their number or mobilize them into tumors could improve outcomes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Carcinoma de Células de Merkel Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Carcinoma de Células de Merkel Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos