Abstract

Aim: To assess the longitudinal pattern of pro-inflammatory cytokines and growth factors in serum up to 1 year following treatment for head and neck cancer.Materials and Methods: Patients with newly diagnosed, curable head and neck cancer were included (n = 30). The most common subsite was oropharynx (n = 13) followed by oral cavity (n = 9). Blood was drawn from all patients at regular intervals (before treatment, 7 weeks after the start of the treatment, and at 3 months and 1 year after termination of treatment) and analyzed for cytokines (Il-1β, Il-2, Il-4, Il-5, Il-6, Il-8, Il-10, GM-CSF, TNF-α, and IFN-γ) and growth factors (G-CSF, FGF-2, EGF, and VEGF).Results: The time point of the peak level of pro-inflammatory cytokines was 7 weeks after start of treatment which corresponded for the majority of patients with termination of radiotherapy or chemoradiotherapy. Patients undergoing chemoradiotherapy exhibited a significant increase of IL-1β, IL-6, and IL-10 at 7 weeks as compared to pre-treatment levels. At 1 year after termination of treatment four patients experienced recurrence of disease while 26 patients were considered disease-free. The patients with recurrence had significantly higher levels of IL-1β, IL-6, IL-8, and IL-10 at 7 weeks after the start of treatment than patients without recurrence. Correlated with T stadium patients with T3-T4 had higher levels of IL-1β and IL-8 than patients with T1-T2 7 weeks after the start of treatment.Conclusions: The observed immune response in this explorative study demonstrates that chemoradiotherapy may induce not only a local treatment effect on the immune system but also effects far outside the irradiated field. The result of the study indicates that analysis of a pro-inflammatory panel of cytokines in serum at 7 weeks after the start of treatment could be of prognostic value in patients with head and neck cancer. Further study of a larger cohort could help identify patients at larger risk for recurrent disease with measurements of pro-inflammatory cytokines under and after treatment.

Highlights

  • Over the last decade knowledge in cancer immunology has grown impressively

  • A mainstay of head and neck cancer treatment is external beam radiotherapy which is known to have the capacity to induce a local and systemic immune response [2]. This complex immune response is regulated among others by pro-inflammatory cytokines in the socalled inflammasomes, cytosolic multiprotein complexes, which have been associated with both carcinogenesis and treatment response in head and neck cancer [3, 4]

  • When patients were stratified to three treatment groups patients undergoing chemoradiotherapy exhibited an increase of IL-1β, interleukin 6 (IL-6), and IL-10 at 7 weeks

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Summary

Introduction

Over the last decade knowledge in cancer immunology has grown impressively. Its clinical application in the management of head and neck cancer is still rather poorly explored but the growth of scientific publications is increasing. A mainstay of head and neck cancer treatment is external beam radiotherapy which is known to have the capacity to induce a local and systemic immune response [2]. This complex immune response is regulated among others by pro-inflammatory cytokines in the socalled inflammasomes, cytosolic multiprotein complexes, which have been associated with both carcinogenesis and treatment response in head and neck cancer [3, 4]. At a local level the immune response is known to give rise to a cytotoxic effect and eradicate tumor cells, but at a systemic level the immune system can contribute to increased side effects. Data about the immune response induced by chemoradiation is scarce in clinical trials

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