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

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.

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