Background: Head and neck squamous cell carcinoma (HNSCC) represents a common cancer worldwide. Past therapeutic advances have not significantly improved HNSCC prognosis. Therefore, it is necessary to further stratify HNSCC, especially with recent advances in tumor immunology.Methods: Tissue microarrays were assembled from tumor tissue samples and were complemented with comprehensive clinicopathological data of n = 419 patients. H&E whole slides from resection specimen (n = 289) were categorized according to their immune cell infiltrate as “hot,” “cold,” or “excluded.”Results: Investigating tumor immune cell patterns, we found significant differences in survival rates. Immunologic “hot” and “excluded” HNSCCs are associated with better overall survival than “cold” HNSCC patients (p < 0.05). Interestingly, the percentage of all three patterns is nearly identical in p16 positive and negative HNSCCs.Conclusions: Using a plain histological H&E approach to categorize HNSCC as being immunologic “hot,” “cold,” or “excluded” can offer a forecast of patients' prognosis and may thus aid as a potential prognostic tool in routine pathology reports. This “hot-cold-excluded” scheme needs to be applied to more HNSCC cohorts and possibly to other cancer types to determine prognostic meaning, e.g., regarding OS or DFS. Furthermore, our cohort reflects epidemiological data in the national, European, and international context. It may, therefore, be of use for future HNSCC characterization.
Background: The approval of immune checkpoint inhibitors in combination with specific diagnostic biomarkers presents new challenges to pathologists as tumor tissue needs to be tested for expression of programmed death-ligand 1 (PD-L1) for a variety of indications. As there is currently no requirement to use companion diagnostic assays for PD-L1 testing in Germany different clones are used in daily routine. While the correlation of staining results has been tested in various entities, there is no data for head and neck squamous cell carcinomas (HNSCC) so far.Methods: We tested five different PD-L1 clones (SP263, SP142, E1L3N, 22-8, 22C3) on primary HNSCC tumor tissue of 75 patients in the form of tissue microarrays. Stainings of both immune and tumor cells were then assessed and quantified by pathologists to simulate real-world routine diagnostics. The results were analyzed descriptively and the resulting staining pattern across patients was further investigated by principal component analysis and non-negative matrix factorization clustering.Results: Percentages of positive immune and tumor cells varied greatly. Both the resulting combined positive score as well as the eligibility for certain checkpoint inhibitor regimens was therefore strongly dependent on the choice of the antibody. No relevant co-clustering and low similarity of relative staining patterns across patients was found for the different antibodies.Conclusions: Performance of different diagnostic anti PD-L1 antibody clones in HNSCC is less robust and interchangeable compared to reported data from other tumor entities. Determination of PD-L1 expression is critical for therapeutic decision making and may be aided by back-to-back testing of different PD-L1 clones.
Eighteen patients with recent ischemic stroke were compared with an equal number of matched controls. Standardized suspensions of red cells as well as of red and white cells were filtered in a new filtration apparatus capable of discriminating between cell deformability and filter occlusion. Results show that red cell deformability, although slightly lower than in controls, is not significantly altered in stroke patients. Filter occlusion, however, was significantly higher in patients when red and white cell suspensions were filtered, but not when red cell suspensions were used, suggesting that white cell filterability is impaired after stroke, which could be due to decreased deformability and/or increased adhesiveness of leukocytes. Slowed white cell passage may also occur in the living microcirculation and may present an obstacle to nutritive flow in exchange vessels, possibly contributing to local ischemia and tissue necrosis after stroke. (Stroke 1987;18:59-62) B RAIN perfusion depends on the flow properties of blood. 1 Particularly on the capillary level and in low flow states, blood cell deformability might be a limiting factor for nutritive flow and oxygen supply.2 Red cell deformability as measured by filtration has been reported to be reduced following ischemic stroke.3 However, this parameter is known to be sensitive to leukocyte effects. 4 At present the mechanical properties of leukocytes in stroke patients are unknown. Since they could contribute to tissue ischemia, 5 the present research investigated the filterability of white cells in patients who recently had suffered an ischemic stroke. Subjects and MethodsEighteen patients (11 women, 7 men) with a history of recent ischemic stroke were randomly selected from our stroke rehabilitation units. Average age was 61 ± 4 years. The acute event dated back 3-4 months and had in all cases been confirmed by computerized tomography (CT) scan during the acute phase. Concomitant diseases or cardiovascular risk factors were hypertension (n = 7), hyperlipoproteinemia (n = 2), smoking (n = 5), and diabetes (n = 3). One patient had suffered a myocardial infarction 4 years earlier and 1 had a history of claudication. Controls consisted of 18 patients matched for age (60 ± 5 years), sex (10 women, 8 men), and concomitant diseases or cardiovascular risk factors: hypertension (n = 8), hyperlipoproteinemia (n = 3), smoking (n = 4), and diabetes (n = 4). There were 2 individuals with a history of myocardial infarction and 2 suffering from claudication. Average body mass index was 26 in patients and 25 in controls.
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