Definitive chemoradiation alters the immunologic landscape and immune checkpoints in head and neck cancer

Vishwajith Sridharan, Danielle N. Margalit, Stephanie A. Lynch, Mariano Severgnini, Jun Zhou, Nicole G. Chau, Guilherme Rabinowits, Jochen H. Lorch, Peter S. Hammerman, F. Stephen Hodi, Robert I. Haddad, Roy B. Tishler, Jonathan D. Schoenfeld*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)252-260
Number of pages9
JournalBritish Journal of Cancer
Volume115
Issue number2
DOIs
StatePublished - Jul 12 2016
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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