For the development and evaluation of new head and neck squamous cell carcinoma (HNSCC) therapeutics, suitable, well-characterized animal models are needed. Thus, by analyzing orthotopic versus subcutaneous models of HNSCC in immunocompetent mice, we evaluated the existence of adenosine-related immunosuppressive B- and T lymphocyte populations within the tumor microenvironment (TME). Applying the SCC VII model for the induction of HNSCC in immunocompetent C3H/HeN mice, the cellular TME was characterized after tumor initiation over time by flow cytometry. The TME in orthotopic grown tumors revealed a larger population of tumor-infiltrating lymphocytes (TIL) with more B cells and CD4⁺ T cells than the subcutaneously grown tumors. Immune cell populations in the blood and bone marrow showed a rather distinct reaction toward tumor induction and tumor location compared to the spleen, lymph nodes, or thymus. In addition, large numbers of immunosuppressive B- and T cells were identified within the TME but also in secondary lymphoid organs, independently of the tumor initiation site. The altered immunogenic TME may influence the response to any treatment attempt. Moreover, when analyzing the TME and other lymphoid organs of tumor-bearing mice, we observed conditions reflecting largely those of patients suffering from HNSCC suggesting the C3H/HeN mouse model as a suitable tool for studies aiming to target immunosuppression to improve anti-cancer therapies.

Background: The impact of demographic change on the age at diagnosis in German head and neck cancer (HNC) patients is unclear. Here we present an evaluation of aging trends in HNC at a tertiary referral center. Methods: Retrospective cohort study on aging trends at the initial diagnosis of newly diagnosed patients with HNC between 2004 and 2018 at the head and neck cancer center Ulm in relation to demographic data of the catchment area. Results: The study population consisted of 2450 individuals diagnosed with HNC with a mean age of 62.84 (±11.67) years. We observed a significant increase in annual incidence rates and mean age over time. Mean age among HNC patients increased significantly more than among the population in the catchment area. Whereas the incidence rate of patients <50 years did not change, the incidence of HNC patients aged ≥70 years increased the most. The mean patient age in the main tumor sites increased significantly. Surprisingly, HPV-positive patients were not younger than HPV-negative patients, but showed a non-significant trend towards a higher mean age (63.0 vs. 60.7 years). Conclusions: Increasing incidence rates in older patients pose a challenge for health care systems. A nationwide study is needed to assess the dynamics and impact of aging on the incidence of HNC.

Introduction: The analysis of exhaustion marker expression, like immune checkpoint molecules (ICMs) on tumor-infiltrating lymphocytes as well as peripheral immune cells of patients with head and neck squamous cell carcinoma (HNSCC), is of high interest since it reveals information about the patient’s immune status and the effectiveness of immune modulation. However, data regarding age-dependent expression are lacking. Here, we demonstrate an increase in most ICMs associated with age and disease, suggesting immune checkpoint modulation as an evidence-based option for the treatment of aged HNSCC patients. Material and Methods: Peripheral blood mononuclear cells (PBMCs) (healthy: n = 30 with an age range from 21 to 84 years/HNSCC: n = 37 with an age range from 37 to 94 years) were analyzed via flow cytometry following (density gradient separation) standard protocol. Flow cytometry was performed using CD4 and CD8 as backbone markers as well as co-stimulatory molecules like CD137, OX40, GITR, and CD27 or ICM like PD-1, CTLA4, BTLA, LAG3, or TIM3 using a Gallios flow cytometer (Beckman Coulter, Brea, CA, USA). Results: We found a statistically significant decreased ICM expression on the PBMCs of healthy donors with increasing age. However, the expression of ICMs in HNSCC was significantly increased (PD1 on CD4⁺ T cells: p = 0.001), while we found a decreased co-stimulatory molecule expression (e.g., CD27 on CD4⁺ T cells and CD39⁺ T cells: p = 0.003 and p = 0.009, respectively). Immune cells of HPV^neg HNSCC have a significant age-dependent decrease in CD27 expression on CD8⁺, CD4⁺, and CD39⁺ T cells (p = 0.0426, p = 0.0078, and p = 0.0078, respectively). Conclusions: This study sheds light on the changing co-stimulatory molecule/ICM expression regarding the patient’s age and reveals an increase in most immune checkpoint molecules for HNSCC patients according to their age. This new evidence is valuable in ensuring individualized therapeutic approaches in the increasingly relevant field of checkpoint inhibition, even in old age.

While recent advances in immuno-oncology have revolutionized cancer therapy, only a subset patients benefit from these treatments and achieve durable clinical responses. Biomarker-guided identification of patients likely to respond to immunotherapy could enable more effective management of various malignancies. To explore this, we took advantage of a Phase I trial evaluating the efficacy of antigen-engineered dendritic cell (DC) vaccine, administered either as monotherapy or in combination with high-dose interferon-α2b, in promoting anti-tumor immunity in melanoma patients. Liquid biopsies, including serum and peripheral blood mononuclear cells, and tumor biopsies were previously analyzed for predictive markers using Luminex, NanoString gene expression profiling and flow cytometry. Here, in vitro stimulation assays were conducted to assess arginase-1 production by circulating myeloid subsets. Of 73 serum analytes, serum arginase-1 (sArg1) most effectively distinguished melanoma patients with measurable disease from healthy donors. Elevated sArg1 levels in patients with active disease correlated with favorable responses to the vaccine and were associated with longer overall and progression-free survival. Integrated phenotypic, functional and metabolic analyses identified circulating CD14^-CD11c⁺ DC3 as the likely source of sArg1. These findings support the hypothesis that sArg1 may serve as a biomarker for responsiveness to cancer vaccine immunotherapy and reflect systemic myeloid cell fitness associated with enhanced anti-tumor immunity. Given the stability and accessibility of serum compared to cells or tissues, this assay could offer a method for assessing patient status, potentially improving stratification and clinical decision-making.

Background: Transforming healthcare related work processes through digitization may help to address the growing demands placed on employees by enhancing user satisfaction and may have an impact on patient safety and treatment quality. Hereby, different approaches reaching from multimodal, workflow-specific systems to more uniform and comprehensive formats have been introduced. Objectives: To date, few comparative studies have examined different Health Information System (HIS) approaches from the perspective of healthcare workers. This study aims to evaluate perceived usability, quality, and compliance of two distinct clinical HIS types. Methods: In this cross-sectional, bicentric study, we compared a multimodal HIS platform with a variation of different digital systems to a uniform, customized HIS solution that was specifically programmed for Otorhinolaryngology, across two university hospital departments in Germany. A total of n = 57 participants (physicians and nurses) completed a 61-item standardized questionnaire. Group differences were analyzed using the Mann-Whitney U test. Results: Healthcare professionals using the multimodal HIS reported significantly lower overall satisfaction, perceived patient safety and treatment quality compared to those using the customized HIS. The latter system was also rated more positively regarding usability and workflow support. Currently, particularly in Germany, significant efforts are needed across all hierarchical levels to establish a cohesive and clear digital HIS with inter-professional, -institutional, -sectional abilities. Conclusion: Our study highlights the perceived advantages of a more uniform and customized HIS from the user’s perspective in healthcare, suggesting that these systems could enhance both staff satisfaction and the quality of care.