Peripheral Cytokine Levels Differ by HPV Status and Change Treatment-Dependently in Patients with Head and Neck Squamous Cell Carcinoma

Abstract

Cytokines and immune mediators play an important role in the communication between immune cells guiding their response to infectious diseases or cancer. In this study, a comprehensive longitudinal analysis of serum cytokines and immune mediators in head and neck squamous cell carcinoma (HNSCC) patients was performed. In a prospective, non-interventional, longitudinal study, blood samples from 22 HNSCC patients were taken at defined time points (TP) before, during, and every 3 months after completion of (chemo)radio)therapy (CRT/RT) until 12 months after treatment. Serum concentrations of 17 cytokines/immune mediators and High-Mobility-Group-Protein B1 (HMGB1) were measured by fluorescent bead array and ELISA. Concentrations of sFas were significantly elevated during and after CRT/RT, whereas perforin levels were significantly decreased after CRT/RT. Levels of MIP-1β and Granzyme B differed significantly during CRT/RT by HPV status. Increased HMGB1 levels were observed at recurrence, accompanied by high levels of IL-4 and IL-10. The sFas increase and simultaneous perforin decrease may indicate an impaired immune cell function during adjuvant radiotherapy. Increased levels of pro-inflammatory cytokines in HPV+ compared to HPV− patients seem to reflect the elevated immunogenicity of HPV-positive tumors. High levels of HMGB1 and anti-inflammatory cytokines at recurrence may be interpreted as a sign of immune evasion.

Prospective longitudinal study of immune checkpoint molecule (ICM) expression in immune cell subsets during curative conventional therapy of head and neck squamous cell carcinoma (HNSCC)

“…This notion is supported by increased levels of mainly inhibitory cytokines in the peripheral blood (IRECT‐001: IL10, IRECT‐006 and IRECT‐018: IL4) at the time of recurrent disease (data not shown). In some patients, a sharp increase of High Mobility Group Box 1 (IRECT‐001, ‐013, ‐017, ‐018), known to act immunosuppressively on T cells, 42,43 was measured around the time of disease recurrence as previously published 9 . A recently published study using single cell RNA sequencing of peripheral and intratumoral lymphocytes indicates that the coexpression of LAG3 and TIM3 inhibits CD4 T cells to develop into T follicular helper cells and instead may promote development into a suppressive phenotype 24 …”

“…Within the prospective noninterventional clinical study titled “Immune Response Evaluation to Curative conventional Therapy (IRECT)” (NCT03053661), systematic immune monitoring was performed longitudinally during conventional treatment of locoregionally advanced HNSCC 9 . Here, we present flow cytometry data assessing nine ICM on peripheral T and B cells from patients harvested during the course of curative treatment and follow‐up.…”

Serum Proteomics in Patients with Head and Neck Cancer: Peripheral Blood Immune Response to Treatment

“…Cytokine levels in HNC have been studied in several previous works using different analytical techniques [ 16 , 54 ]. Dickinson et al used mass spectrometry to differentiate proteins in sera from HPV-positive and HPV-negative patients, and found that three proteins were expressed differently [ 55 ].…”

Dynamics of HMBG1 (High Mobility Group Box 1) during radiochemotherapy correlate with outcome of HNSCC patients

“…However, the authors indicate a low specificity. In this study, HMGB1 was measured only once during radiotherapy [ 36 ]. To further evaluate the potential of this biomarker in patients with HNSCC, we investigated HMGB1 in weekly sampling during definitive radiochemotherapy and during follow-up in a homogenous cohort of patients undergoing curative definitive radiochemotherapy for locally advanced HNSCC.…”