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Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.
Darragh, Laurel B; Nguyen, Alexander; Pham, Tiffany T; Idlett-Ali, Shaquia; Knitz, Michael W; Gadwa, Jacob; Bukkapatnam, Sanjana; Corbo, Sophia; Olimpo, Nicholas A; Nguyen, Diemmy; Van Court, Benjamin; Neupert, Brooke; Yu, Justin; Ross, Richard B; Corbisiero, Michaele; Abdelazeem, Khalid N M; Maroney, Sean P; Galindo, David C; Mukdad, Laith; Saviola, Anthony; Joshi, Molishree; White, Ruth; Alhiyari, Yazeed; Samedi, Von; Van Bokhoven, Adrie; St John, Maie; Karam, Sana D.
Afiliación
  • Darragh LB; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA; Department of Immunology and Microbiology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Nguyen A; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Pham TT; Department of Otolaryngology - Head and Neck Surgery, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Idlett-Ali S; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Knitz MW; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Gadwa J; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Bukkapatnam S; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Corbo S; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Olimpo NA; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Nguyen D; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Van Court B; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Neupert B; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Yu J; Department of Otolaryngology - Head and Neck Surgery, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Ross RB; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Corbisiero M; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Abdelazeem KNM; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA; Radiation Biology Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
  • Maroney SP; Department of Biochemistry and Molecular Genetics, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Galindo DC; Department of Biochemistry and Molecular Genetics, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Mukdad L; Department of Head & Neck Surgery, University of California, Los Angeles, Los Angeles, CA, USA.
  • Saviola A; Department of Biochemistry and Molecular Genetics, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Joshi M; Department of Pharmacology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • White R; Department of Medicine, Columbia University, New York, NY, USA.
  • Alhiyari Y; Department of Head & Neck Surgery, University of California, Los Angeles, Los Angeles, CA, USA.
  • Samedi V; Department of Pathology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • Van Bokhoven A; Department of Pathology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
  • St John M; Department of Head & Neck Surgery, University of California, Los Angeles, Los Angeles, CA, USA.
  • Karam SD; Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA; Department of Immunology and Microbiology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA. Electronic address: sana.karam@cuanschutz.edu.
Med ; 5(3): 254-270.e8, 2024 Mar 08.
Article en En | MEDLINE | ID: mdl-38423011
ABSTRACT

BACKGROUND:

Perineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth.

METHODS:

We used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system.

FINDINGS:

Calcitonin gene-related peptide (CGRP) directly inhibited CD8 T cell activity in vitro, and blocking sensory nerve function surgically, pharmacologically, or genetically increased CD8 and CD4 T cell activity in vivo.

CONCLUSIONS:

Our data support sensory nerves playing a role in accelerating tumor growth by directly acting on the adaptive immune system to decrease Th1 CD4 T cells and activated CD8 T cells in the TME. These data support further investigation into the role of sensory nerves in the TME of HNSCC and points toward the possible treatment efficacy of blocking sensory nerve function or specifically inhibiting CGRP release or activity within the TME to improve outcomes.

FUNDING:

1R01DE028282-01, 1R01DE028529-01, 1P50CA261605-01 (to S.D.K.), 1R01CA284651-01 (to S.D.K.), and F31 DE029997 (to L.B.D.).
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Péptido Relacionado con Gen de Calcitonina / Neoplasias de Cabeza y Cuello Límite: Animals / Humans Idioma: En Revista: Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Péptido Relacionado con Gen de Calcitonina / Neoplasias de Cabeza y Cuello Límite: Animals / Humans Idioma: En Revista: Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos