gms | German Medical Science

Background: Immunological biomarkers are becoming increasingly important in the classification and treatment of head and neck cancer (HNSCC). These markers include the expression of immune checkpoint molecules, but also various immune cell (sub)types. However, HNSCC not only interact with the immune system of the tumor tissue, but also induces systemic effects that can be additionally influenced by other factors such as the patient’s microbiome. Nevertheless, reliable immunological biomarkers that predict treatment response and outcome in HNSCC patients are lacking. In order to define predictive and prognostic biomarkers for HNSCC, the prospective and multicentric ImmunBioKHT study was initiated. Here, not only samples from the tumor tissue, but also from the patient's peripheral blood and microbiome are examined and correlated with the clinical outcome.

Materials and methods: Approval from the institutional review board of the Friedrich-Alexander-Universität Erlangen-Nürnberg was granted in December 2021 (# 21-440-B). By now, more than 150 patients have been enrolled in the intervention cohort. Trial registration number is NCT05375266. For the determination of a longitudinal immune status from peripheral blood, a flow cytometry-based assay is applied. Thus, blood is taken before and 7 days after the tumor surgery, as well as after the adjuvant or definitive radio-chemotherapy (RCT). The serum and plasma of the patients is used for further analyses of soluble immune modulators. Further, potential markers on the metabolome and microbiome are obtained from saliva, stool and tumor swab samples. From the excised tumor tissue a detailed histology and tumor grading, as well as the determination of common immunological markers is performed. All patients signed a “broad consent”. All samples are stored at Central Biobank Erlangen (CeBE), partner site Biobank Radiation Oncology.

Results: In this first interims analysis, we present the data of the immune monitoring from the peripheral blood of 150 patients. We found that the tumor surgery is already inducing significant modulations of the peripheral immune system. In detail, the cell counts of monocytes and granulocytes, as well as the activation status of various immune cell types was regulated. Further modulations occurred after RCT, such as an expected significant decrease of cells of the adaptive immune system, but also a modulation of the activation markers of T cells and monocytes. In addition, we could show, that low density neutrophilic granulocytes showed an elevated degranulation ability after the surgery indicating a potential neutrophil-platelet aggregation.

Conclusion: The here presented interims analysis shows that the standard therapy of HNSCC leads to significant modifications of the immune system. Those modulations need to be connected to the biological tumor activity in the future in order to define predictive and prognostic immunological biomarkers for HNSCC.