The rapid expansion and application of nanoparticles in medicine has meanwhile contributed to a large number of experimental and clinical studies, especially in cancer research. Numerous different fields within nanomedicine have now become established more clearly. These are based on the one hand on the properties of different types of nanoparticles (chemical, physical, and biological) and on the other hand on the possible specific applications such as drug carrier, radioenhancer, in vivo monitoring of drug distribution within the tumor, or tumor-specific immune-modulating effects. Nanoparticles can also be functionalized by multiple properties potentiating their intrinsic antitumoral effects, such as coupling of antibodies to address target tissue or coupling to chemotherapeutic agents. In this work, an up-to-date overview of the developments and applications related to nanoparticles in head and neck cancer is given.

Die rasante Verbreitung und Anwendung von Nanopartikeln in der Medizin haben zu einer Vielzahl von experimentellen und klinischen Studien insbesondere in der onkologischen Forschung beigetragen. Innerhalb dieser sog. Nanomedizin haben sich unterschiedliche Schwerpunkte etabliert. Diese orientieren sich zum einen an den chemischen, physikalischen und biologischen Eigenschaften unterschiedlichster Nanopartikel und zum anderen an den möglichen spezifischen Anwendungen wie beispielsweise Medikamententransport, Strahlentherapie, In-vivo-Monitoring von Wirkstoffen im Tumor oder auch immunmodulierende Wirkungen. Nanopartikel können zudem funktionalisiert werden, indem bestimmte Faktoren wie Antikörper zur spezifischen Adressierung eines Zielgewebes oder die Kopplung von Chemotherapeutika die intrinsische antitumorale Wirkung von Nanopartikeln potenzieren. In der vorliegenden Arbeit wird ein aktueller Überblick über die Entwicklungen und Anwendungen von Nanopartikeln in der Kopf-Hals-Onkologie gegeben.

Introduction Patients with HPV- localized head and neck cancer show distinct therapeutic responses compared to HPV-associated cancers, implicating differences in immune status and immune response. Therefore, we analyzed immune profiles of myeloid-derived suppressor cells (MDSC) in HPV+versus HPV- disease and their influence on CD8+T cells.

Patients with HPV--localized head and neck cancer (HNC) show inferior outcomes after surgery and radiochemotherapy compared to HPV-associated cancers. The underlying mechanisms remain elusive, but differences in immune status and immune activity may be implicated. In this study, we analyzed immune profiles of CD8+ T cells and myeloid-derived suppressor cells (MDSC) in HPV+ versus HPV- disease.The overall frequency of CD8+ T cells was reduced in HNC versus healthy donors but substantially increased after curative therapy (surgery and/or radiochemotherapy). In HPV+ patients, this increase was associated with significant induction of peripheral blood CD8+/CD45RA-/CD62L- effector memory cells. The frequency of HPV-antigen-specific CD8+ cells was low even in patients with virally associated tumors and dropped to background levels after curative therapy. Pre-therapeutic counts of circulating monocytic MDSC, but not PMN-MDSC, were increased in patients with HPV- disease. This increase was accompanied by reduced fractions of terminally differentiated CD8+ effector cells. HPV- tumors showed reduced infiltrates of CD8+ and CD45RO+ immune cells compared with HPV+ tumors. Importantly, frequencies of tumor tissue-infiltrating PMN-MDSC were increased, while percentages of Granzyme B+ and Ki-67+ CD8 T cells were reduced in patients with HPV- disease.We report differences in frequencies and relative ratios of MDSC and effector T cells in HPV- HNC compared with more immunogenic HPV-associated disease. Our data provide new insight into the immunological profiles of these two tumor entities and may be utilized for more tailored immunotherapeutic approaches in the future.

Hintergrund Immunregulatorische Mechanismen des Tumormilieus beeinflussen den Tumorprogress und das Ansprechen auf sowohl konventionelle als auch immunmodulierende Therapien. Regulatorische T Zellen (Tregs) repräsentieren eine wesentliche Komponente dieser Mechanismen. Im Folgenden untersuchen wir den Einfluss der PD1/ PDL1 Signalwege auf regulatorische T Zellen von Kopf-Halskarzinompatienten (HNC).

Background Immunoregulatory mechanisms in the tumor microenvironment influence tumor progression and therapeutic response for both conventional therapies as well as immunomodulatory strategies. Regulatory T cells represent a key component for these mechanisms. Here, we investigate the influence of PD1/PD-L1 signaling on regulatory T cells of HNSCC patients. Experimental setting: Blood samples of HNC patients were collected. Isolation of CD4+ T cells was performed through negative selection with an enrichment kit. Cells were labeled with the proliferation marker CFSE. After stimulation with CD3/CD28 beads (control) or CD3/CD28/PDL1 beads over 5 days, cells were stained for CD3 (APC-Cy7), CD4 (PE-TR), CD25 (PE-Cy7), CD39 (APC), PD1 (PerCP-Cy5.5) and Tim3 (Brilliant Violet 421). A comparison of proliferation rates and surface markers was performed through flow cytometry

Introduction In particular, aggressive salivary gland tumors such as salivary duct carcinoma (SDC), adenocarcinoma NOS (ANOS), and adenoid cystic carcinoma (ACC) more often lead to unresectable local recurrences and distant metastases and thus the need for systemic tumor therapy. Analysis of treatable molecular alterations and immunologic processes of the tumor and surrounding stroma may help improve patient prognosis.

Einführung Insbesondere bei aggressiven Speicheldrüsentumoren wie dem Speichelgangkarzinom (SDC), dem Adenokarzinom NOS (ANOS) und dem Adenoidzystischen Karzinom (ACC) kommt es häufiger zu inoperablen Lokalrezidiven und Fernmetastasen und somit der Notwendigkeit einer systemischen Tumortherapie. Eine Analyse der therapierbaren molekularen Veränderungen und immunologischen Prozesse des Tumors und des umgebenden Stromas könnte dazu beitragen, die Prognose der Patienten zu verbessern. Patienten und Methoden Unsere Studie untersuchte die Expression von LAG3 insbesondere in SDC (n=14), ANOS (n=27) und ACC (n=34). Die Schnitte wurden mittels anti-LAG3 IgG sowie CD8 und TP53 monoklonalen Antikörpern gefärbt. Die Expression wurde mit den pathologischen Eigenschaften und dem Follow-up der Patienten korreliert.

Supplementary Figure S1 shows identification of different subsets of PD1+ cells

Supplementary figure S1: IL-10, IL-1RA and Eotaxin plasma concentration in patients pre- vs. post-treatment with Cetuximab plus motolimod. Supplementary table S1: 95% confidence interval for figure 5 comparing pre vs post treatment expression changes of TIGIT, PD-1, CTLA-4 and CD27.

Supplementary figure S1 & supplementary table S1 legends

Legends for Supplementary figures and table

Einleitung Die Bedeutung der neutrophilen Granulozyten für die Krebsentstehung und Tumorzell-elimination ist bislang unzureichend untersucht. Im Vorliegenden untersuchen wir neutrophile Helfer-Zellen (NBH) und deren Einfluss auf B-Zell-Eigenschaften in regionären Lymphknoten (RLN) von Kopf-Hals-Karzinom (HNC) Patienten.

Head and Neck Cancers (HNCs) have highly immunosuppressive properties. Small extracellular vesicles (sEVs), including exosomes, nanosized mediators of intercellular communication in the blood, carry immunosuppressive proteins and effectively inhibit anti-tumor immune responses in HNCs. This study evaluates immunosuppressive markers on sEVs from 40 HNC patients at different disease stages and 3- and 6-month follow-up after surgery and/or chemoradiotherapy. As controls, sEVs from normal donors (NDs) are examined. Immunoregulatory surface markers on sEVs were detected as relative fluorescence intensity (RFI) using on-bead flow cytometry, and their expression levels were monitored in the early and late stages of HNC and during follow-up. In parallel, the sEV-mediated apoptosis of CD8+ Jurkat cells was assessed. Together with TGF-β1 and PD-L1 abundance, total sEV proteins are elevated with disease progression. In contrast, total sEV protein, including TGF-β1, PD-1 and PD-L1, decrease upon therapy response during follow-up. Overall survival analysis implies that high sEV PD-1/PD-L1 content is an unfavorable prognostic marker in HNC. Consistently, the sEV-mediated induction of apoptosis in CD8+ T cells correlates with the disease activity and therapy response. These findings indicate that a combination of immunoregulatory marker profiles should be preferred over a single marker to monitor disease progression and therapy response in HNC.

Immune checkpoint inhibitors (CPI) are the standard of care in patients (pts) failing platinum-based therapy for recurrent or metastatic head and neck cancer (r/m SCCHN). Here we explored the overall clinical impact of CPI in two real-world patient cohorts.

Einleitung Tumor-infiltrierende Lymphozyten (TIL) sind in den letzten Jahren in den Mittelpunkt onkologischer Forschung gerückt.Wesentliche Forschungsansätze neuer immunologischer Therapien zielen auf die Beeinflussung der TIL ab, um eine effektive Antitumorale Wirkung zu erreichen. Zur Analyse der TIL werden verschiedene Methoden zur Isolation für weitergehende Untersuchungen (FACS, ELISA, etc.) verwendet.