Comparison of the Composition of Lymphocyte Subpopulations in Non-relapse and Relapse Patients With Squamous Cell Carcinoma of the Head and Neck Before, During Radiochemotherapy and in the Follow-up Period: a Multicenter Prospective Study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

Abstract

Background: Radiochemotherapy (RCT) has been shown to induce changes in immune cell homeostasis which might affect antitumor immune responses. In the present study, we aimed to compare the composition and kinetics of major lymphocyte subsets in the periphery of patients with non-locoregional recurrent (n=23) and locoregional recurrent (n=9) squamous cell carcinoma of the head and neck (SCCHN) upon primary RCT.Methods: EDTA-blood of non-locoregional recurrent SCCHN patients was collected before (t0), after application of 20 to 30 Gy (t1), in the follow-up period 3 (t2) and 6 months (t3) after RCT. In patients with locoregional recurrence blood samples were taken at t0, t1, t2 and at the time of recurrence (t5). EDTA-blood of age-related, healthy volunteers (n=22) served as a control (Ctrl). Major lymphocyte subpopulations were phenotyped by multiparameter flow cytometry.Results: Patients with non-recurrent SCCHN had significantly lower proportions of CD19+ B cells compared to healthy individuals before start of any therapy (t0) that dropped further until 3 months after RCT (t2), but reached initial levels 6 months after RCT (t3). The proportion of CD3+ T and CD3+/CD4+ T helper cells continuously decreased between t0 and t3, whereas that of CD8+ cytotoxic T cells and CD3+/CD56+ NK-like T cells (NKT) gradually increased in the same period of time in non-recurrent patients. The percentage of CD4+/CD25+/FoxP3+ regulatory T cells (Tregs) decreased directly after RCT, but increased above initial levels in the follow-up period 3 (t2) and 6 (t3) months after RCT. Patients with locoregional recurrence showed similar trends with respect to B, T cells and Tregs between t0 and t5. CD4+ T helper cells remained stably low between t0 and t5 in patients with locoregional recurrence compared to Ctrl. NKT/NK cell subsets (CD56+/CD69+, CD3-/CD56+, CD3-/CD94+, CD3-/NKG2D+, CD3-/NKp30+, CD3-/NKp46+) increased continuously up to 6 months after RCT (t0-t3) in patients without locoregional recurrence, whereas in patients with locoregional recurrence, these subsets remained stably low until time of recurrence (t5).Conclusion: Monitoring the kinetics of lymphocyte subpopulations especially activatory NK cells before and after RCT might provide a clue with respect to the development of an early locoregional recurrence in patients with SCCHN. However, studies with larger patient cohorts are needed.

DNA methylation‐derived systemic inflammation indices and their association with oropharyngeal cancer risk and survival

“…Cell‐mediated immunity plays an essential role in response to inflammation and presence of a tumor. Patients with HNSCC have previously been reported to have decreased absolute counts of lymphocytes, 13,48,49 while an increased number of peripheral blood monocytes 50,51 and neutrophils 51,52 also have been reported to characterize head and neck cancer and other cancer types. We observed an elevated mdNLR and decreased mdLMR in this head and neck cancer case group, similar to these prior findings.…”