Polyfunctionality of CD4+ T lymphocytes is increased after chemoradiotherapy of head and neck squamous cell carcinoma

Strahlenther Onkol. 2018 May;194(5):392-402. doi: 10.1007/s00066-018-1289-z. Epub 2018 Apr 16.

Abstract

Background: For head and neck squamous cell cancer (HNSCC), standard therapy consists of surgery, radiation, and/or chemotherapy. Antineoplastic immunotherapy could be an option in an adjuvant setting and is already in palliation. A functional immune system is a prerequisite for successful immunotherapy. However, effects of the standard-of-care therapy on the patients' immune system are not fully understood.

Methods: Peripheral blood mononuclear cells (PBMC) were collected from patients with HNSCC (n = 37) and healthy controls (n = 10). PBMC were stimulated with staphylococcal enterotoxin B (SEB). Simultaneous expression of various cytokines was measured in CD4+ and CD8+ T cells by multicolor flow cytometry, and polyfunctional cytokine expression profiles were determined on a single-cell basis.

Results: Expression levels of all measured cytokines in CD4+ T cells were higher in patients after chemoradiotherapy (CRT) as compared to untreated HNSCC patients or normal controls. After CRT, the frequency of polyfunctional CD4+ T cells, which simultaneously expressed multiple cytokines, was significantly increased as compared to untreated patients (p < 0.01).

Conclusion: CRT increases polyfunctionality of CD4+ T cells in HNSCC patients, suggesting that standard-of-care therapy can promote immune activity in immune cells. These polyfunctional CD4+ T cells in the blood of treated HNSCC patients are expected to be responsive to subsequent immunotherapeutic approaches.

Keywords: Cancer; Cytokines; Immune system; Immunotherapy; Response.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / radiation effects*
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy*
  • Combined Modality Therapy
  • Cytokines / blood
  • Female
  • Flow Cytometry
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / radiation effects
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Otorhinolaryngologic Neoplasms / immunology*
  • Otorhinolaryngologic Neoplasms / pathology
  • Otorhinolaryngologic Neoplasms / therapy*

Substances

  • Cytokines