Differential impact of TIM-3 ligands on NK cell function.

Background: The transmembrane protein T-cell immunoglobulin and mucin-domain containing molecule 3 (TIM-3) is an immune checkpoint receptor that is expressed by a variety of leukocyte subsets, particularly in the tumor microenvironment. An effective TIM-3-targeting therapy should account for multiple biological factors, including the disease setting, the specific cell types involved and their varying sensitivities to the four putative TIM-3 ligands (galectin-9, phosphatidylserine, high mobility group protein B1 and carcinoembryonic antigen cell adhesion molecule 1), each of which engages a unique binding site on the receptor's variable immunoglobulin domain. The primary objectives of this study were to assess the prevalence and function of TIM-3 natural killer (NK) cells in patients with head and neck squamous cell carcinoma (HNSCC), determine whether the four TIM-3 ligands differentially affect TIM-3 NK cell functions, identify the most immunosuppressive ligand, and evaluate whether targeting ligand-mediated TIM-3 signaling enhances NK cell effector functions.

Safety and Tolerability of Home Infusions in Down Syndrome Regression Disorder.

Purpose: Down syndrome regression disorder (DSRD) is a rare neuropsychiatric condition affecting otherwise healthy individuals with Down syndrome. Multiple studies on DSRD have revealed that immunotherapy with intravenous immunoglobulin (IVIg) is both safe and effective, although site of infusion has never been studied. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD receiving home-based infusions.

CD8 Tumor-Infiltrating Lymphocytes in Head and Neck Cancer: A Review.

CD8 tumor-infiltrating lymphocytes (TILs) are increasingly used in oncology as a prognostic and predictive tool to guide patient management. This review summarizes current literature on CD8 TILs in head and neck squamous cell carcinoma (SCC). Published meta-analyses and clinical trials evaluating CD8 TILs were analyzed.

Morphine treatment restricts response to immunotherapy in oral squamous cell carcinoma.

Background: Immune checkpoint inhibitors (ICIs) are becoming the standard of care for recurrent and metastatic cancer. Opioids, the primary treatment for cancer-related pain, are immunosuppressive raising concerns about their potential to interfere with the efficacy of ICIs. We hypothesize that exogenous opioids given for analgesia suppress antitumor immunity via T cell-mediated mu opioid receptor 1 (OPRM1) signaling.

Impact of post-operative transoral robotic surgery hemorrhage on adjuvant treatment delays in patients with oropharyngeal squamous cell carcinoma.

Objectives: Transoral robotic surgery (TORS) for the treatment for oropharyngeal squamous cell carcinoma (SCC) carries a risk of post-operative hemorrhage. Increased time from surgery to completion of adjuvant therapy has been associated with decreased survival. Our objective was to assess for adjuvant treatments delays in patients with post-operative bleeding.

Small extracellular vesicles as biomarkers of response in recurrent/metastatic HNSCC patients treated with immunotherapy.

Background: Biomarkers that effectively predict response to anti-PD-1 mAb therapy in cancer patients are an unmet need. We evaluated the utility of small extracellular vesicles (sEV) as biomarkers of response to immunotherapy in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients.

Methods: Plasma sEV were isolated from 24 R/M HNSCC patients prior to immunotherapy initiation.

Association of Patient and Tumor Characteristics With Outcomes in Young Head and Neck Squamous Cell Carcinoma Patients.

Introduction: We retrospectively studied young patients with head and neck squamous cell carcinoma (HNSCC) to identify factors associated with disease-specific survival (DSS).

Methods: Patient and tumor characteristics of patients aged ≤45 who received treatments for non-metastatic HNSCC were collected to identify factors associated with DSS. Proportional hazards regression was applied separately for surgical and non-surgical patients.

Intraoperative Pathology Consultation in Patients With p16-Positive Unknown Primary Squamous Cell Carcinoma.

Importance: Current guidelines recommend intraoperative frozen section(s) during diagnostic surgery for squamous cell carcinoma for unknown primary tumors (SCCUP).

Objective: To determine the utility of intraoperative pathology consultation during transoral robotic surgery (TORS) in localizing primary tumors and influencing need for adjuvant therapy.

Design, Setting, And Participants: A retrospective case series including 47 adult patients with human papillomavirus (HPV)-associated SCCUP who underwent TORS/oropharyngectomy between January 2016 and February 2023 was carried out at a single tertiary care hospital.

Neoadjuvant immunotherapy for head and neck squamous cell carcinoma.

The neoadjuvant immunotherapy approach marks a significant shift in the treatment paradigm of potentially curable HNSCC. Here, current therapies, despite being highly individualized and advanced, often fall short in achieving satisfactory long-term survival rates and are frequently associated with substantial morbidity.The primary advantage of this approach lies in its potential to intensify and enhance treatment regimens, offering a distinct modality that complements the existing triad of surgery, radiotherapy, and chemotherapy.

Th2 Cells Are Associated with Tumor Recurrence Following Radiation.

The curative treatment of multiple solid tumors, including head and neck squamous cell carcinoma (HNSCC), utilizes radiation. The outcomes for HPV/p16-negative HNSCC are significantly worse than HPV/p16-positive tumors, with increased radiation resistance leading to worse locoregional recurrence (LRR) and ultimately death. This study analyzed the relationship between immune function and outcomes following radiation in HPV/p16-negative tumors to identify mechanisms of radiation resistance and prognostic immune biomarkers.

All-trans retinoic acid induces durable tumor immunity in IDH-mutant gliomas by rescuing transcriptional repression of the CRBP1-retinoic acid axis.

Diffuse gliomas are epigenetically dysregulated, immunologically cold, and fatal tumors characterized by mutations in isocitrate dehydrogenase (IDH). Although IDH mutations yield a uniquely immunosuppressive tumor microenvironment, the regulatory mechanisms that drive the immune landscape of IDH mutant (IDHm) gliomas remain unknown. Here, we reveal that transcriptional repression of retinoic acid (RA) pathway signaling impairs both innate and adaptive immune surveillance in IDHm glioma through epigenetic silencing of retinol binding protein 1 (RBP1) and induces a profound anti-inflammatory landscape marked by loss of inflammatory cell states and infiltration of suppressive myeloid phenotypes.

International guidelines for intratumoral and intranodal injection of NBTXR3 nanoparticles in head and neck cancers.

Background: An international multidisciplinary panel of experts aimed to provide consensus guidelines describing the optimal intratumoral and intranodal injection of NBTXR3 hafnium oxide nanoparticles in head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, and cervical lymph nodes and to review data concerning safety, feasibility, and procedural aspects of administration.

Methods: The Delphi method was used to determine consensus. A 4-member steering committee and a 10-member monitoring committee wrote and revised the guidelines, divided into eight sections.

Over 132 Years Ago, the Inaugural Immunotherapy Treated Its First Head and Neck Cancer Patient.

Immunotherapy in oncology has a more extensive history than is commonly perceived. Rooted in the observations and experiences of multiple physicians in the late 19th century, immunological interventions are currently integral to the oncological therapeutic repertoire. This article seeks to delineate the evolution of cancer immunotherapy, tracing its inception in 1891 with the pioneering work of an American surgeon, William B.

The role of surgery and deescalation for HPV-related oropharyngeal cancer.

Recently published and ongoing trials are helping to define the role of transoral robotic surgery for oropharyngeal cancer. Evidence to date supports the use of surgery as a valuable tool in the multidisciplinary deescalation of low-risk human papillomavirus-related oropharyngeal squamous cell carcinoma.

Final results of urelumab, an anti-CD137 agonist monoclonal antibody, in combination with cetuximab or nivolumab in patients with advanced solid tumors.

Background: Resistance to immune checkpoint inhibitors and targeted treatments for cancer is common; thus, novel immunotherapy agents are needed. Urelumab is a monoclonal antibody agonist that binds to CD137 receptors expressed on T cells. Here, we report two studies that evaluated urelumab in combination with cetuximab or nivolumab in patients with select, advanced solid tumors.

Treatment package time < 14 weeks improves recurrence free and disease specific survival in HPV positive OPC with high-risk features.

Background: Guidelines recommend treatment package time < 85 days and time from surgery to radiation initiation < 6 weeks in head and neck cancer patients. However, HPV positive primaries treated with TORS and adjuvant radiotherapy traditionally demonstrate favorable outcomes.

Methods: Single center retrospective chart review of patients diagnosed with HPV positive treatment naïve primary squamous cell carcinoma treated with TORS and postoperative radiation therapy with or without Chemotherapy from 2012 to 2022 with data collection from December 2022-April 2023.

Xevinapant plus radiotherapy in resected, high-risk, cisplatin-ineligible LA SCCHN: the phase III XRay Vision study design.

There is a significant unmet need and lack of treatment options for patients with resected, high-risk, cisplatin-ineligible locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Xevinapant, a first-in-class, potent, oral, small-molecule IAP inhibitor, is thought to restore cancer cell sensitivity to chemotherapy and radiotherapy in clinical and preclinical studies. We describe the design of XRay Vision (NCT05386550), an international, randomized, double-blind, phase III study.

Genomic and transcriptomic analysis of cutaneous squamous cell carcinoma arising in immunocompetent and immunosuppressed patients.

Background: Cutaneous squamous cell carcinoma (cSCC) is the most common skin malignancy arising in immunocompromised patients such as solid organ transplant recipients. In addition to an abundance in number, the morbidity and mortality of these tumors in this patient population exceeds that of immune competent individuals. Here, we used whole exome and bulk RNA sequencing to analyze mutation profiles between tumors arising in immunocompetent and immunosuppressed patients.

Integrated BATF transcriptional network regulates suppressive intratumoral regulatory T cells.

Human regulatory T cells (T) are crucial regulators of tissue repair, autoimmune diseases, and cancer. However, it is challenging to inhibit the suppressive function of T for cancer therapy without affecting immune homeostasis. Identifying pathways that may distinguish tumor-restricted T is important, yet the transcriptional programs that control intratumoral T gene expression, and that are distinct from T in healthy tissues, remain largely unknown.

Test-retest repeatability for Fatigue Assessment Scale, Short-Form 6-Dimension and King's Sarcoidosis Questionnaire in people with sarcoidosis associated fatigue.

Background And Aim: Patient related outcomes are important in sarcoidosis but the medium-term repeatability of the key patient reported outcome measure is not known. We aimed to test the repeatability of the Fatigue Assessment Scale (FAS), Short Form 6-Dimension (SF-6D), and King's Sarcoidosis Questionnaire (KSQ) in free living people with sarcoidosis associated fatigue.

Methods: Twelve people with sarcoidosis associated fatigue completed the FAS, short form 36 questionnaire (SF-36) and the KSQ at baseline and 12 weeks.

Tumor cell p38 inhibition to overcome immunotherapy resistance.

Patients with tumors that do not respond to immune-checkpoint inhibition often harbor a non-T cell-inflamed tumor microenvironment, characterized by the absence of IFN-γ-associated CD8 T cell and dendritic cell activation. Understanding the molecular mechanisms underlying immune exclusion in non-responding patients may enable the development of novel combination therapies. p38 MAPK is a known regulator of dendritic and myeloid cells however a tumor-intrinsic immunomodulatory role has not been previously described.