title: Definitive chemoradiation alters the immunologic landscape and immune checkpoints in head and neck cancer.
abstract: Preclinical and clinical studies suggest potential synergy between high dose per fraction focal radiation and immunotherapy. However, conventionally fractionated radiation regimens in combination with concurrent chemotherapy are more commonly administered to patients as definitive treatment and may have both immune-stimulating and -suppressive effects.
  
  
  
  We prospectively collected longitudinal samples from head and neck squamous cell carcinoma patients receiving definitive radiation therapy. We quantified changes in populations of circulating immune cells and chemokines CXCL9, 10, and 16. Analyses of humoral and cellular immune responses were conducted in select patients via proteomic analysis and T-cell receptor sequencing.
  
  
  
  Treatment not only increased circulating CD-8+ T-effector cells, but also myeloid-derived suppressor cells, regulatory T cells, and checkpoint receptor-expressing T cells, particularly PD-1+ T cells. Significant decreases in CXCL10 and increases in CXLC16 were noted. Treatment also increased the percentage of unique and dominant TCR clones, and increased humoral responses as measured by proteomic array.
  
  
  
  Our results suggest that fractionated chemoradiation leads to quantifiable effects in circulating immune mediators, including a balance of stimulatory and suppressive mechanisms. These results suggest future combinations with immune checkpoint blockade.
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA, USA.|Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA, USA.
authors.forename: Vishwajith
authors.initials: V
authors.lastname: Sridharan
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA, USA.
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Margalit
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Lynch
authors.affiliation: Center for Immuno-oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Mariano
authors.initials: M
authors.lastname: Severgnini
authors.affiliation: Center for Immuno-oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA, USA.
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Chau
authors.affiliation: Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA, USA.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Rabinowits
authors.affiliation: Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA, USA.
authors.forename: Jochen H
authors.initials: JH
authors.lastname: Lorch
authors.affiliation: Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Hammerman
authors.affiliation: Center for Immuno-oncology, Dana-Farber Cancer Institute, Boston, MA, USA.|Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA, USA.
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.affiliation: Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA, USA.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Haddad
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA, USA.
authors.forename: Roy B
authors.initials: RB
authors.lastname: Tishler
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Schoenfeld
mesh_terms: D000917:Antibody Formation; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000628:therapy*; D059248:Chemoradiotherapy; D016207:Cytokines / Q000097:blood; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D016207:Cytokines