Immunohistochemical Profiling of IDO1 and IL4I1 in Head and Neck Squamous Cell Carcinoma: Interplay for Metabolic Reprogramming?

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous and malignant disease with a limited number of biomarkers and insufficient targeted therapies. The current therapeutic landscape is challenged by low response rates, underscoring the need for new therapeutic targets. The success of immunotherapy in HNSCC has highlighted the importance of the immune microenvironment, and since metabolic reprogramming, especially altered tryptophan metabolism, is an important aspect in immune evasion, the interplay of the two enzymes IDO1 and IL4I1 was investigated in HNSCC to assess their immunosuppressive roles and potential as prognostic biomarkers.

Prognostic Value of SOX2 and NANOG Expression in Recurrent Oral Squamous Cell Carcinoma.

Background: Recurrent oral squamous cell carcinoma (re-OSCC) poses a serious therapeutic challenge and is linked to poor survival outcomes. SOX2 and NANOG, key transcription factors in cancer stem cell biology, may drive tumor progression and therapy resistance. However, their prognostic value in re-OSCC and their relationship to adjuvant therapy remain unclear.

Tumor budding and lymphovascular invasion as prognostic factors in p16-positive oropharyngeal squamous cell carcinomas.

Background: We aimed to validate the prognostic significance of tumor budding (TB) in p16-positive oropharyngeal squamous cell carcinomas (OPSCC).

Methods: We analyzed digitized H&E-stained slides from a multicenter cohort of five large university centers consisting of n = 275 cases of p16-positive OPSCC. We evaluated TB along with other histological parameters (morphology, tumor-stroma-ratio, lymphovascular invasion (LVI), perineural invasion) and calculated survival outcomes using both univariate and multivariate analyses.

Correction: Becker et al. Identifying Predictive Biomarkers for Head and Neck Squamous Cell Carcinoma Response. 2023, , 5597.

In the original publication [...

Identifying Predictive Biomarkers for Head and Neck Squamous Cell Carcinoma Response.

The 5-year survival rate for head and neck squamous cell carcinoma (HNSCC) is approximately 65%. In addition to radio-chemotherapy, immunotherapy is an approach in the treatment of advanced HNSCC. A better understanding of the immune context would allow personalized treatment by identifying patients who are best suited for different treatment options.

Correlation of Intra-tumoral and Peripheral PD-1/PD-L1 Immunity in Head and Neck Cancer.

Background/aim: Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous malignant disease of the oral cavity, pharynx, and larynx. HNSCC cells evade the host immune system through alterations in their immunogenicity, production of immunosuppressive mediators, and induction of immunomodulatory cell types. The immune status of solid HNSCC can be considered as hot, cold, or excluded for each patient individually, based on the distribution of tumor infiltrating immune cells.

Prognostic impact of the loss of E-cadherin and expression of N-cadherin at the invasive front of primary and recurrent oral squamous cell carcinoma.

The epithelial-mesenchymal transition (EMT) is a biological mechanism in multiple pathophysiological diseases. Related alterations in cadherin expression play a crucial role in carcinogenesis, progression, angiogenesis, and immune response. EMT cells exhibit a transition from an epithelial to a mesenchymal phenotype (cadherin-switch).

TRIM21 Expression as a Prognostic Biomarker for Progression-Free Survival in HNSCC.

Patients with head and neck squamous cell carcinoma (HNSCC) continue to have a rather poor prognosis. Treatment-related comorbidities have negative impacts on their quality of life. TRIM21 is a cytosolic E3 ubiquitin ligase that was initially described as an autoantigen in autoimmune diseases and later associated with the intracellular antiviral response.

DNA methylation-based classification of sinonasal tumors.

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles.

Deglycosylation of pathological specimens alters performance of diagnostic PDL1 antibodies.

Immunohistochemical (IHC) predictive quantitation of PDL1 expression is obligatory in many cancer entities with improved response to immune checkpoint inhibition in PDL1-positive subgroups. With recent demonstration of increased positivity rates after enzymatic deglycosylation in breast cancer specimens, a comparative analysis with two different antibodies and extended controls was performed in a cohort of head and neck squamous cell cancer samples (HNSCC).Formalin-fixed paraffin-embedded tissue from HNSCC specimens was used for initial on-slide method optimization based on the PNGase F assay.

TRIM24 Expression as an Independent Biomarker for Prognosis and Tumor Recurrence in HNSCC.

Background: Head and neck squamous cell carcinomas (HNSCCs) are among the most common cancers in humans worldwide and have a rather poor prognosis. TRIM24 has various intracellular functions and was identified in other cancer entities as a poor prognostic factor for patients.

Methods: The expression of TRIM24 was evaluated by using immunohistochemistry.

Increased Abundances of CD16 Non-Classical Monocytes Accompany with Elevated Monocytic PD-L1 and CD4 T Cell Disturbances in Oropharyngeal Cancer.

Background: Patients with human papilloma virus (HPV)-related oropharyngeal cancer have a better prognosis than nonvirally associated patients, most likely because of better immune responses. Increased infiltration of T lymphocytes into the oropharyngeal tumor tissue has been observed, but the dynamics of circulating lymphocytes and monocytes are not fully understood. The aim of this study was to understand the population dynamics of circulating monocyte subsets in oropharyngeal cancer (OPC) patients with regard to the clinicopathological parameters and accompanying immunological consequences in view of the CD4/CD8 T cell subset composition, and the expression of checkpoint pathway proteins programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1).

Elevated LSD1 and SNAIL Expression Indicate Poor Prognosis in Hypopharynx Carcinoma.

Head and neck squamous cell carcinomas (HNSCC) are among the most common cancers worldwide and are associated with a poor prognosis for patients. Among HNSCC, those originating in the hypopharynx have the worst prognosis. The histone demethylase LSD1 has been shown to promote cancer initiation, progression, and relapse through various mechanisms and is upregulated in many cancer tissues.

CDK7 Predicts Worse Outcome in Head and Neck Squamous-Cell Cancer.

HNSCC is the sixth most common cancer worldwide and the prognosis is still poor. Here, we investigated the prognostic implications of CDK7 and pMED1. Both proteins affect transcription, and their expression is altered throughout different tumor entities.

Therapy-Related Transcriptional Subtypes in Matched Primary and Recurrent Head and Neck Cancer.

Purpose: The genetic relatedness between primary and recurrent head and neck squamous cell carcinomas (HNSCC) reflects the extent of heterogeneity and therapy-driven selection of tumor subpopulations. Yet, current treatment of recurrent HNSCC ignores the molecular characteristics of therapy-resistant tumor populations.

Experimental Design: From 150 tumors, 74 primary HNSCCs were RNA sequenced and 38 matched primary/recurrent tumor pairs were both whole-exome and RNA sequenced.

Spatial Distribution of Immune Cells in Head and Neck Squamous Cell Carcinomas.

Background: Head and neck squamous cell carcinomas (HNSCCs) have a very moderate response rate to immune checkpoint inhibitor (ICI) treatment compared to other cancer types. Lacking predictive markers for treatment response, we analyzed the immune status of HNSCC and assessed the spatial distribution of immune cells.

Materials And Methods: assessing hematoxylin-eosin (H&E) stains, we divided HNSCCs by the immune cell distribution in hot, cold, and excluded tumors.

Delta-Like Protein 3 Expression in Paired Chemonaive and Chemorelapsed Small Cell Lung Cancer Samples.

Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate directed against Delta-like protein 3 (DLL3), is under development for patients with small cell lung cancer (SCLC). DLL3 is expressed on the majority of SCLC samples. Because SCLC is rarely biopsied in the course of disease, data regarding DLL3 expression in relapses is not available.

Development and reliability of the histological THROMBEX-classification rule for thrombotic emboli of acute ischemic stroke patients.

Background: Thrombus histology has become a potential diagnostic tool for the etiology assessment of patients with ischemic stroke caused by embolic proximal vessel occlusion. We validated a classification rule that differentiates between cardiac and arteriosclerotic emboli in individual stroke patients. We aim to describe in detail the development of this classification rule and disclose its reliability.

IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies: Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome.

IDH2 R172 mutations occur in sinonasal undifferentiated carcinoma (SNUC), large-cell neuroendocrine carcinoma (LCNEC), sinonasal adenocarcinomas, and olfactory neuroblastoma (ONB). We performed a clinical, pathologic, and genetic/epigenetic analysis of a large IDH2-mutated sinonasal tumor cohort to explore their distinct features. A total 165 sinonasal/skull base tumors included 40 IDH2 mutants studied by light microscopy, immunohistochemistry, and genome-wide DNA methylation, and 125 IDH2 wild-type tumors used for comparison.

Palliative Local Radiotherapy for Advanced Squamous Cell Carcinoma of the Head-and-Neck: Prognostic Factors of Survival.

Background/aim: A considerable number of patients with advanced head-and-neck cancer (SCCHN) receive palliative radiotherapy. This study aimed to identify prognostic factors for survival to facilitate personalized treatment for these patients.

Patients And Methods: Ninety-two patients receiving palliative radiotherapy for SCCHN were retrospectively analyzed.

A New Survival Score for Patients Scheduled for Palliative Irradiation of Locally Advanced Carcinoma of the Head-and-Neck.

Background/aim: Patients with advanced squamous cell carcinoma of the head-and-neck (SCCHN) may be assigned to palliative irradiation. A survival score was developed for this group to support treatment personalization.

Patients And Methods: Seventy-eight patients who received palliative irradiation for SCCHN and had complete data regarding performance score, pre-radiotherapy hemoglobin levels, and main tumor site were included in this retrospective study.

Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma.

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.

First approach to distinguish between cardiac and arteriosclerotic emboli of individual stroke patients applying the histological THROMBEX-classification rule.

Endovascular treatment of strokes caused by large vessel occlusion enables the histopathological investigation of the retrieved embolus, possibly providing a novel opportunity to contribute to the diagnostic workup of etiology and to define secondary prevention measures in strokes with uncertain genesis. We aimed to develop a classification rule based on pathophysiological considerations and adjustment to reference thrombi for distinction between cardiac and arteriosclerotic emboli and to validate this classification rule on a patient cohort. From 125 patients with stroke due to large vessel occlusion and thrombectomy, 82 patients with known etiology (55 cardioembolic and 27 arterioembolic strokes) were included.

Immunologic "Cold" Squamous Cell Carcinomas of the Head and Neck Are Associated With an Unfavorable Prognosis.

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.