Changes in the tumor microenvironment in recurrent head and neck squamous cell carcinoma and its implication on efficacy of immune checkpoint inhibitors.

Little is known about changes in the abundance of tumor-infiltrating lymphocytes (TILs) and immune phenotype (IP) in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). We aimed to compare the TILs and IP between initial and recurrent HNSCCs using paired analysis. Thirty-seven patients who experienced recurrence after surgical resection and received treatment with immune checkpoint inhibitors (ICIs) between June 2014 and June 2023 were included.

Developmental trajectory of unconventional T cells of the cynomolgus macaque thymus.

As nonhuman primates are immunologically the closest model to humans, a comprehensive understanding of T-cell development in these species is crucial. However, the differentiation pathways in which thymocytes participate, along with their heterogeneity, remain poorly characterized. Using single-cell RNA sequencing, we thoroughly profiled the development of various T-cell lineages in the juvenile cynomolgus monkey thymus, identifying and characterizing 12 distinct thymic cell states or types.

The Modified S-GRAS Scoring System for Prognosis in Korean with Adrenocortical Carcinoma.

Backgruound: Adrenocortical carcinomas (ACCs) are rare tumors with aggressive but varied prognosis. Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score, based on clinical and pathological factors, was found to best stratify the prognosis of European ACC patients. This study assessed the prognostic performance of modified S-GRAS (mS-GRAS) scores including modified grade (mG) by integrating mitotic counts into the Ki67 index (original grade), in Korean ACC patients.

Diagnostic Accuracy of Preoperative Radiologic Findings in Papillary Thyroid Microcarcinoma: Discrepancies with the Postoperative Pathologic Diagnosis and Implications for Clinical Outcomes.

Backgruound: The diagnostic accuracy of preoperative radiologic findings in predicting the tumor characteristics and clinical outcomes of papillary thyroid microcarcinoma (PTMC) was evaluated across all risk groups.

Methods: In total, 939 PTMC patients, comprising both low-risk and non-low-risk groups, who underwent surgery were enrolled. The preoperative tumor size and lymph node metastasis (LNM) were evaluated by ultrasonography within 6 months before surgery and compared with the postoperative pathologic findings.

CRIF1 deficiency induces FOXP3 inflammatory non-suppressive regulatory T cells, thereby promoting antitumor immunity.

Recently identified human FOXP3CD45RA inflammatory non-suppressive (INS) cells produce proinflammatory cytokines, exhibit reduced suppressiveness, and promote antitumor immunity unlike conventional regulatory T cells (T). In spite of their implication in tumors, the mechanism for generation of FOXP3CD45RA INS cells in vivo is unclear. We showed that the FOXP3CD45RA cells in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator.

Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes.

Context: Clinical implications of unilateral primary aldosteronism (PA) histopathology remain to be determined in various ethnic populations.

Objective: We examined the histopathology of unilateral PA using CYP11B2 immunostaining in relation to clinical phenotypes and postsurgical outcomes.

Methods: Patients consecutively operated for unilateral PA from 2010 to 2020 at 3 tertiary hospitals in South Korea were retrospectively enrolled.

IL-4/IL-4 Ab complex enhances the accumulation of both antigen-specific and bystander CD8 T cells in mouse lungs infected with influenza A virus.

Background: Unlike conventional T cells, innate and virtual-memory CD8 T cells in naïve mice acquire their memory phenotypes and functions in the absence of antigenic encounters in a cytokine-dependent manner. The relevant cytokines include interleukin-4 (IL-4), type I interferon, and interleukin-15 (IL-15). Moreover, exogenous IL-4 can also induce de novo generation and/or expansion of the virtual-memory CD8 T cell population.

De novo fatty-acid synthesis protects invariant NKT cells from cell death, thereby promoting their homeostasis and pathogenic roles in airway hyperresponsiveness.

Invariant natural-killer T (NKT) cells play pathogenic roles in allergic asthma in murine models and possibly also humans. While many studies show that the development and functions of innate and adaptive immune cells depend on their metabolic state, the evidence for this in NKT cells is very limited. It is also not clear whether such metabolic regulation of NKT cells could participate in their pathogenic activities in asthma.

Prevention of severe lung immunopathology associated with influenza infection through adeno-associated virus vector administration.

Background: Influenza A viruses (IAVs) have long posed a threat to humans, occasionally causing significant morbidity and mortality. The initial immune response is triggered by infected epithelial cells, alveolar macrophages and dendritic cells. However, an exaggerated innate immune response can result in severe lung injury and even host mortality.

Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes as a biomarker in locally advanced unresectable thymic epithelial neoplasm: A single-center, retrospective, longitudinal cohort study.

Background: Thymic epithelial tumors (TET) are rare malignancies and lack well-defined biomarkers for neoadjuvant therapy. This study aimed to evaluate the clinical utility of artificial intelligence (AI)-powered tumor-infiltrating lymphocyte (TIL) analysis in TET.

Methods: Patients initially diagnosed with unresectable thymoma or thymic carcinoma who underwent neoadjuvant therapy between January 2004 and December 2021 formed our study population.

CD1b glycoprotein, a crucial marker of thymocyte development during T cell maturation in cynomolgus monkeys.

Phenotypic markers that denote different developmental stages of thymocytes are important for understanding T cell development in the thymus. Here, we show that CD1b is a critical discriminator of thymocyte maturation stage in cynomolgus monkeys. CD1b was expressed by immature thymocytes prior to β-selection, and its expression decreased as cells became fully mature in the thymus.

Assessment of Esophageal Reconstruction via Bioreactor Cultivation of a Synthetic Scaffold in a Canine Model.

Objectives: Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals that requires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment of peristalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaffold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model.

Molecular Classification of Extrapulmonary Neuroendocrine Carcinomas With Emphasis on POU2F3-positive Tuft Cell Carcinoma.

Extrapulmonary neuroendocrine carcinomas (EP-NECs) are associated with a poor clinical outcome, and limited information is available on the biology and treatment of EP-NECs. We studied EP-NECs by applying the recent novel findings from studies of pulmonary neuroendocrine carcinomas, including POU2F3, the master regulator of tuft cell variant of small cell lung carcinomas. A cohort of 190 patients with surgically resected EP-NECs or poorly differentiated carcinomas (PDCs) were established.

Heterogeneity of circulating CD4CD8 double-positive T cells characterized by scRNA-seq analysis and trajectory inference.

The frequency of CD4CD8 double-positive (DP) T cells is highly associated with a variety of diseases. Recently, we used high-throughput single-cell RNA sequencing to show that circulating DP T cells in cynomolgus monkeys comprise nine heterogeneous populations. To better understand the characteristics of DP T cells, we analyzed 7601 cells from a rhesus monkey and detected 14,459 genes.

Characteristics of Intraoperative Hemodynamic Instability in Postoperatively Diagnosed Pheochromocytoma and Sympathetic Paraganglioma Patients.

Background: Despite an improved understanding of pheochromocytoma and extra-adrenal sympathetic parganglioma (PPGL), including diagnosis and management, some PPGLs are postoperatively diagnosed. Clinical characteristics and intraoperative haemodynamic instability (HI) in postoperatively diagnosed PPGL patients have been poorly defined. Thus, we investigated the clinical characteristics and HI in patients with postoperatively diagnosed PPGLs compared to patients with preoperatively diagnosed PPGLs.

A sinonasal yolk sac tumor in an adult.

Yolk sac tumors (YSTs), which are also called endodermal sinus tumors, are malignant tumors of germ cell origin. These tumors usually occur in the gonads, but 20% of cases have been reported at extragonadal sites. The head and neck is a rarely affected region that accounts for just 1% of all malignant tumors of germ cell origin.

Cellular heterogeneity of circulating CD4CD8 double-positive T cells characterized by single-cell RNA sequencing.

Circulating CD4CD8 double-positive (DP) T cells are associated with a variety of disease states. However, unlike conventional T cells, the composition of this population is poorly understood. Here, we used single-cell RNA sequencing (scRNA-seq) to analyze the composition and characteristics of the DP T cell population circulating in the peripheral blood of cynomolgus monkeys.

Expression of CYP11B1 and CYP11B2 in adrenal adenoma correlates with clinical characteristics of primary aldosteronism.

Objective: Primary aldosteronism (PA) shows histological heterogeneity and clinical variability, including the coexistence of hypercortisolemia. Immunohistochemical analyses of steroidogenic enzymes in adrenal tissues have provided new insights into the pathogenesis of PA. However, a comprehensive analysis of the association between enzyme expression and clinical characteristics of PA has rarely been conducted.

Ssu72 phosphatase directly binds to ZAP-70, thereby providing fine-tuning of TCR signaling and preventing spontaneous inflammation.

ZAP-70 is required for the initiation of T cell receptor (TCR) signaling, and Ssu72 is a phosphatase that regulates RNA polymerase II activity in the nucleus. However, the mechanism by which ZAP-70 regulates the fine-tuning of TCR signaling remains elusive. Here, we found that Ssu72 contributed to the fine-tuning of TCR signaling by acting as tyrosine phosphatase for ZAP-70.

Mass Spectrometry-Based Proteomic Discovery of Prognostic Biomarkers in Adrenal Cortical Carcinoma.

Adrenal cortical carcinoma (ACC) is an extremely rare disease with a variable prognosis. Current prognostic markers have limitations in identifying patients with a poor prognosis. Herein, we aimed to investigate the prognostic protein biomarkers of ACC using mass-spectrometry-based proteomics.

NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake.

BACKGROUNDMolecular characterization in pediatric papillary thyroid cancer (PTC), distinct from adult PTC, is important for developing molecularly targeted therapies for progressive radioiodine-refractory (131I-refractory) PTC.METHODSPTC samples from 106 pediatric patients (age range: 4.3-19.