m1A inhibition fuels oncolytic virus-elicited antitumor immunity via downregulating MYC/PD-L1 signaling.

N1-methyladenosine (m1A) RNA methylation is critical for regulating mRNA translation; however, its role in the development, progression, and immunotherapy response of head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Using Tgfbr1 and Pten conditional knockout (2cKO) mice, we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels. Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis. Mechanistically, TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis, upregulating programmed death-ligand 1 (PD-L1) expression. Moreover, m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus (oHSV), contributing to reactive PD-L1 upregulation. Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth, representing a promising strategy to alleviate resistance. These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression, providing a mutually reinforcing combination immunotherapy approach.

A Network Meta-Analysis of the Systemic Therapies in Unresectable Head and Neck Squamous Cell Carcinoma.

The current standard treatment for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) comprises concurrent radiotherapy (CRT) alongside platinum-based chemotherapy. However, innovative therapeutic alternatives are being evaluated in phase II/III randomized trials. This study employed a Bayesian network meta-analysis (NMA) using fixed effects to provide both direct and indirect comparisons of all existing treatment modalities for unresectable LASCCHN. METHODS: We referenced randomized controlled trials (RCTs) from January 2000 to July 2023 by extensively reviewing PubMed, EMBASE, and Web of Science databases, adhering to the Cochrane methodology. Relevant data, including summary estimates of overall survival (OS) and progression-free survival (PFS), were extracted from these selected studies and recorded in a predefined database sheet. Subsequently, we conducted a random effects network meta-analysis using a Bayesian framework. RESULTS: Based on the Surface Under the Cumulative Ranking (SUCRA) values, the league table organizes the various treatments for OS in the following order: IC + RT&MTT, MTT-CRT, IC + CRT&MTT, CRT, IC + CRT, MTT-RT, IC + MTT-RT, and RT. In a similar order, the treatments rank as follows according to the league table: IC + CRT&MTT, MTT-CRT, IC + CRT, IC + RT&MTT, CRT, IC + MTT-RT, MTT-RT, and RT. Notably, none of these treatments showed significant advantages over concurrent chemoradiotherapy. CONCLUSION: Despite concurrent chemoradiotherapy being the prevailing treatment for LASCCHN, our findings suggest the potential for improved outcomes when concurrent chemoradiotherapy is combined with targeted therapy or induction chemotherapy.

The current standard treatment for advanced head and neck cancer involves combining radiation therapy with chemotherapy. However, there are ongoing trials exploring alternative therapies. In this study, we conducted a comprehensive analysis of existing treatments using a statistical method called network meta-analysis. Our analysis included data from randomized controlled trials published between January 2000 and July 2023. We focused on overall survival and progression-free survival as key outcome measures. The results of our analysis showed that none of the alternative treatments demonstrated significant advantages over the standard concurrent chemoradiotherapy. Nevertheless, there is potential for improved outcomes when targeted therapy or induction chemotherapy is combined with concurrent chemoradiotherapy.

Transcriptomic analysis-guided assessment of precision-cut tumor slices (PCTS) as an ex-vivo tool in cancer research.

With cancer immunotherapy and precision medicine dynamically evolving, there is greater need for pre-clinical models that can better replicate the intact tumor and its complex tumor microenvironment (TME). Precision-cut tumor slices (PCTS) have recently emerged as an ex vivo human tumor model, offering the opportunity to study individual patient responses to targeted therapies, including immunotherapies. However, little is known about the physiologic status of PCTS and how culture conditions alter gene expression. In this study, we generated PCTS from head and neck cancers (HNC) and mesothelioma tumors (Meso) and undertook transcriptomic analyses to understand the changes that occur in the timeframe between PCTS generation and up to 72 h (hrs) in culture. Our findings showed major changes occurring during the first 24 h culture period of PCTS, involving genes related to wound healing, extracellular matrix, hypoxia, and IFNγ-dependent pathways in both tumor types, as well as tumor-specific changes. Collectively, our data provides an insight into PCTS physiology, which should be taken into consideration when designing PCTS studies, especially in the context of immunology and immunotherapy.

Quality of life in 583 head and neck cancer survivors assessed with the FACE-Q head and neck cancer module.

OBJECTIVES: Long-term health-related quality of life (HRQOL) is frequently affected in head and neck cancer (HNC) survivors. Due to the shortage of studies investigating long-term patient-reported outcomes, we investigated long-term HRQOL using the novel FACE-Q HNC Module. METHODS: A retrospective cross-sectional single-center study was performed, including all patients who underwent curative treatment for HNC between 2006 and 2013. All eligible patients (n = 863) were invited to participate of whom 540 completed the questionnaires. Additionally, a prospective longitudinal cohort of 43 HNC patients treated between 2020 and 2022 was included who preoperatively filled in the FACE-Q, and at three, six, and 12 months postoperatively. HRQOL domain scores were analyzed to visualize group characteristics by tumor site and type of surgical resection. RESULTS: Both surgical and non-surgical HNC treatments predominantly affected long-term functional HRQOL domains (eating, salivation, speech, and swallowing), eating distress, and speaking distress, with distinct profiles depending on tumor site and type of treatment. In contrast, few long-term intergroup differences between HNC patients were observed for appearance, smiling, drooling distress, and smiling distress. Longitudinal data showed significant deterioration across all functional HRQOL domains in the short-term following treatment. Patients predominantly reported long-lasting negative treatment effects at 12 months follow-up for functional domains, whereas psychological domains showed near-complete recovery at group level. CONCLUSIONS: At long-term, various function-related and psychosocial HRQOL domains still are affected in head and neck cancer survivors. The results may serve to better inform patients with regard to specific treatments and highlight HRQOL domains which may potentially be optimized.

Intratumoral therapies in head and neck squamous cell carcinoma: A systematic review and future perspectives.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) presents an ideal scenario for intratumoral therapies (IT), due to its local recurrence pattern and frequent superficial extension. IT therapies aim to effect tumor regression by directly injecting antineoplastic agents into lesions. However, there is a lack of updated evidence regarding IT therapies in HNSCC. PATIENTS AND METHODS: A systematic literature search (CRD42023462291) was conducted using WebOfScience, ClinicalTrials.gov, and conference abstracts from ESMO and ASCO, identifying for IT clinical trials in patients with HNSCC, from database creation to September 12th, 2023. Efficacy as well as safety (grade ≥ 3 treatment-related adverse events[trAEs]) were reported. RESULTS: After evaluation of 1180 articles identified by the systematic search, 31 studies treating 948 patients were included. IT injectables were categorized as chemotherapies with or without electroporation (k = 4, N = 268), oncolytic viruses, plasmids, and bacteria-based (k = 16, N = 446), immunotherapies and EGFR-based therapies (k = 5, N = 160), radioenhancer particles (k = 2, N = 68), and calcium electroporation (k = 1, n = 6). EGFR-antisense plasmids, NBTXR3 radioenhancer and immune innate agonists show best overall response rates, at 83 %, 81 % and 44 % respectively. Eleven (35 %) studies added systemic therapy or radiotherapy to the IT injections. No study used predictive biomarkers to guide patient selection. 97 % studies were phase I-II. Safety-wise, electroporation and epinephrine-based injectable trials had significant local symptoms such as necrosis, fistula formation and post-injection dysphagia. Treatment-related tumor haemorrhages of various grades were described in several trials. Grade ≥ 3 trAEs attributable to the other therapies mainly comprised general symptoms such as fatigue. There were 3 injectable-related deaths across the systematic review. CONCLUSION: This is the first review to summarize all available evidence of IT in HNSCC. As of today, IT therapies lack sufficient evidence to recommend their use in clinical practice. Continuing research on potential molecules, patient selection, safe administration of injections and controlled randomized trials are needed to assess their added benefit.

[Concurrent simultaneous integrated boost radiotherapy and cetuximab in head and neck squamous cell cancer patients: is it feasible in daily clinical practice?] / Radioterapia a intensità modulata con boost simultaneo più cetuximab in pazienti con carcinoma a cellule squamose in stadio localmente avanzato del distretto testa collo: è fattibile nella pratica clinica quotidiana?

INTRODUCTION AND AIM: Locally advanced head and neck squamous cell carcinoma (LA-Hnscc) is a true therapeutical challenge in the modern era and the scientific community is trying to face this challenge with new therapeutical strategies, including combinations of monoclonal antibodies and radiation therapy. The aim of this study is to evaluate clinical outcomes in LA-Hnscc patients unfit to receive platinum-based chemotherapy, treated with concurrent simultaneous integrated boost-intensity modulated radiotherapy (Sib-Imrt) + cetuximab (Ctx) in daily clinical practice. METHODS: LA-Hnscc patients not included in other prospective studies treated in 4 Italian radiotherapy units (2 Messina, 1 Rome, and 1 Lecce) using Sib-Imrt and Ctx were included in this study. Acute and late toxicities and overall survival (OS) have been evaluated. RESULTS: Data regarding 27 patients with squamous tumour were collected and reviewed. The primary tumour sites were oropharynx in 14 patients (51.9%), oral cavity in 7 (25.9%), larynx in 3 (11%) and other sites in 3(11%). There were 20 (74%) patients had stage IV (16 IVa and 4 IVb). Complete remission was observed in 18 patients (66.7%), a partial remission in 4 (14.8%) whilst 4 had a progression disease (14.8%). After 3 year of follow-up 7/27 patients were deaths. The OS was 95.5%, 62.5% and 52.9% respectively at 1,2 and 3 years. Acute toxicities were observed in all treated patients (mucositis, dermatitis and dysphagia) while 66.7% of patients developed late toxicities. All observed toxicities were grade 1 to 3 and just 1 patient developed a G4 toxicity. CONCLUSION: The concurrent bio-radiotherapy of Sib-Imrt and cetuximab is feasible in real-life daily clinical practice for LA-Hnscc patients unfit for platinum-based chemoradiotherapy.

[Cervical CUP Syndrome: Diagnosis and Therapy]. / Zervikales CUP-Syndrom: Diagnostik und Therapie.

In CUP syndrome (CUP = cancer of unknown primary) there are 1 or more metastases of a primary tumor that cannot be localized despite extensive diagnostics. CUP syndrome accounts for 5% of all human malignancies, making it one of the 10 most common forms of cancer. In addition to inflammatory lymph node enlargement and benign changes such as cervical cysts, lymph node metastases are among the most common cervical masses. Cervical CUP syndrome is a histologically confirmed cervical lymph node metastasis with an unknown primary tumor. In addition to anamnesis, clinical examination and histological confirmation, diagnostics include radiological imaging using PET-CT and panendoscopy with histological primary tumor search. Treatment options include surgical therapy with neck dissection and chemoradiotherapy.

Neoadjuvant immunotherapy for head and neck squamous cell carcinoma. / Neoadjuvante Immuntherapie bei Kopf-Hals- Plattenepithelkarzinomen.

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. Checkpoint inhibitors have been at the forefront of this evolution. Demonstrating moderate yet significant survival benefits in the recurrent-metastatic setting with a relatively better safety profile compared to conventional treatments, these agents hold promise when considered for earlier stages of HNSCC.On the other hand, a significant potential benefit of introducing immunotherapy in the neoadjuvant phase is the possibility of treatment de-escalation. By reducing the tumor burden before surgery, this strategy could lead to less invasive surgical interventions. The prospect of organ-sparing protocols becomes a realistic and highly valued goal in this context. Further, the early application of immunotherapy might catalyze a more effective and durable immune response. The induction of an immune memory may potentially lead to a more effective surveillance of residual disease, decreasing the rates of local, regional, and distant recurrences, thereby enhancing overall and recurrence-free survival.However, neoadjuvant immunotherapy is not without its challenges. One of the primary concerns is the safety and adverse events profile. While data suggest that adverse events are relatively rare and manageable, the long-term safety profile in the neoadjuvant setting, especially in the context of curative intent, remains a subject for ongoing research. Another unsolved issue lies in the accurate assessment of treatment response. The discrepancy between radiographic assessment using RECIST criteria and histological findings has been noted, indicating a gap in current imaging techniques' ability to accurately reflect the true efficacy of immunotherapy. This gap underscores the necessity for improved imaging methodologies and the development of new radiologic and pathologic criteria tailored to evaluate the response to immunotherapy accurately.Treatment combinations and timing represent another layer of complexity. There is a vast array of possibilities in combining immunotherapy agents with conventional chemotherapy, targeted therapy, radiation, and other experimental treatments. Determining the optimal treatment regimen for individual patients becomes an intricate task, especially when comparing small, single-arm, non-randomized trials with varying regimens and outcome measures.Moreover, one needs to consider the importance of pre- and intraoperative decision-making in the context of neoadjuvant immunotherapy. As experience with this treatment paradigm grows, there is potential for more tailored surgical approaches based on the patient's remaining disease post-neoadjuvant treatment. This consideration is particularly relevant in extensive surgeries, where organ-sparing protocols could be evaluated.In practical terms, the multi-modal nature of this treatment strategy introduces complexities, especially outside clinical trial settings. Patients face challenges in navigating the treatment landscape, which involves coordination across multiple medical disciplines, highlighting the necessity for streamlined care pathways at specialized centers to facilitate effective treatment management if the neoadjuvant approach is introduced to the real-world.These potential harms and open questions underscore the critical need for meticulously designed clinical trials and correlational studies to ensure patient safety and efficacy. Only these can ensure that this new treatment approach is introduced in a safe way and fulfils the promise it theoretically holds.

Interdisciplinary Management of Vascular Anomalies in the Head and Neck. / Interdisziplinäres Management vaskulärer Anomalien im Kopf-Hals-Bereich.

Vascular anomalies in the head and neck area are usually rare diseases and pose a particular diagnostic and therapeutic challenge. They are divided into vascular tumours and vascular malformations. A distinction is made between benign tumours, such as infantile haemangioma, and rare malignant tumours, such as angiosarcoma. Vascular malformations are categorised as simple malformations, mixed malformations, large vessel anomalies and those associated with other anomalies. Treatment is interdisciplinary and various modalities are available. These include clinical observation, sclerotherapy, embolisation, ablative and coagulating procedures, surgical resection and systemic drug therapy. Treatment is challenging, as vascular anomalies in the head and neck region practically always affect function and aesthetics. A better understanding of the genetic and molecular biological basis of vascular anomalies has recently led to clinical research into targeted drug therapies. This article provides an up-to-date overview of the diagnosis, clinic and treatment of vascular anomalies in the head and neck region.

Research progress of immunotherapy for advanced head and neck cancer.

Head and neck cancer accounts for about one-fifth of all malignant tumors, and the incidence is increasing year by year. The overall mortality rate was high and the 5-year survival rate was low. At present, the combination of surgery, radiotherapy, and chemotherapy is the main treatment in clinical practice, but the treatment of recurrent or metastatic advanced head and neck cancer is still a challenge. With the rise of immunotherapy, more and more studies on immune checkpoint inhibitors have been conducted. This review summarizes the mechanism, clinical application and safety of immunotherapy for advanced head and neck cancer.

Breaking Ground in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Novel Therapies Beyond PD-L1 Immunotherapy.

The treatment for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with immune checkpoint inhibitors (anti-PD1) with or without chemotherapy has led to an improvement in survival. Yet, despite this therapeutic advancement, only 15%-19% of patients remain alive at four years, highlighting the poor survival and unmet need for improved therapies for this patient population. Some of the key evolving novel therapeutics beyond anti-PD1 in R/M HNSCC have included therapeutic vaccine therapies, bispecific antibodies/fusion proteins and multitargeted kinase inhibitors, and antibody-drug conjugates (ADCs). Multiple concurrent investigations of novel therapeutics for patients with R/M HNSCC beyond anti-PD(L)1 inhibition are currently underway with some promising early results. Beyond immune checkpoint inhibition, novel immunotherapeutic strategies including therapeutic vaccines ranging from targeting human papillomavirus-specific epitopes to personalized neoantigen vaccines are ongoing with some early efficacy signals and large, randomized trials. Other novel weapons including bispecific antibodies, fusion proteins, and multitargeted kinase inhibitors leverage multiple concurrent targets and modulation of the tumor microenvironment to harness antitumor immunity and inhibition of protumorigenic signaling pathways with emerging promising results. Finally, as with other solid tumors, ADCs remain a promising therapeutic intervention either alone or in combination with immunotherapy for patients with R/M HNSCC. With early enthusiasm across novel therapies in R/M HNSCC, results of larger randomized trials in R/M HNSCC are eagerly awaited.

Positive correlation between persistence of medical nutrition therapy and overall survival in patients with head and neck cancer.

Background: Several factors can affect overall survival of head and neck cancer (HNC) patients, including characteristics of the cancer disease and response to treatments. However, patients' nutritional status and the effectiveness of medical nutrition therapy (MNT) can also impact overall survival. The primary goal of our research was to collect real-life data on the use of MNT in HNC patients and to specifically investigate the correlation between survival and the duration of uninterrupted (persistent) nutrition. Method: The data of this retrospective, analytical, cohort study was collected from electronic healthcare records from the Hungarian National Health Insurance Fund Management. Overall, 38,675 HNC patients' data of the period between 2012 and 2021 was used. We applied multi-step exclusions to identify patient groups accurately and to avoid biasing factors. Statistical analysis was done by the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: Throughout the investigated period 16,871 (64%) patients received MNT therapy out of 26,253 newly diagnosed patients (≥18 years). In terms of the persistence of MNT, we divided the patients into three groups (1-3; 4-6; ≥7-month duration of MNT). When comparing these groups, we found that patients receiving long-term (≥7 months) MNT had a significantly longer overall survival (p < 0.0001) than those who received MNT for a shorter duration, both in locally advanced and recurrent/metastatic cases. Conclusion: The main outcome of the study is that there is a positive correlation between the persistence of MNT and the overall survival in HNC patients when nutritional intervention lasts several months. It highlights the responsibility of the specialists during the patient journey to use MNT early and to continue its use for as long as it is beneficial to the patients.

Comprehensive investigation into the influence of glycosylation on head and neck squamous cell carcinoma and development of a prognostic model for risk assessment and anticipating immunotherapy.

Background: It has been well established that glycosylation plays a pivotal role in initiation, progression, and therapy resistance of several cancers. However, the correlations between glycosylation and head and neck squamous cell carcinoma (HNSCC) have not been elucidated in detail. Methods: The paramount genes governing glycosylation were discerned via the utilization of the Protein-Protein Interaction (PPI) network and correlation analysis, coupled with single-cell RNA sequencing (scRNA-seq) analysis. To construct risk models exhibiting heightened predictive efficacy, cox- and lasso-regression methodologies were employed, and the veracity of these models was substantiated across both internal and external datasets. Subsequently, an exploration into the distinctions within the tumor microenvironment (TME), immunotherapy responses, and enriched pathways among disparate risk cohorts ensued. Ultimately, cell experiments were conducted to validate the consequential impact of SMS in Head and Neck Squamous Cell Carcinoma (HNSCC). Results: A total of 184 genes orchestrating glycosylation were delineated for subsequent scrutiny. Employing cox- and lasso-regression methodologies, we fashioned a 3-gene signature, proficient in prognosticating the outcomes for patients afflicted with HNSCC. Noteworthy observations encompassed distinctions in the Tumor Microenvironment (TME), levels of immune cell infiltration, and the presence of immune checkpoint markers among divergent risk cohorts, holding potentially consequential implications for the clinical management of HNSCC patients. Conclusion: The prognosis of HNSCC can be proficiently anticipated through risk signatures based on Glycosylation-related genes (GRGs). A thorough delineation of the GRGs signature in HNSCC holds the potential to facilitate the interpretation of HNSCC's responsiveness to immunotherapy and provide innovative strategies for cancer treatment.

Six-month mortality has decreased for patients with curative treatment intent for head and neck cancer in Sweden.

BACKGROUND: In general, survival outcomes for patients with Head and Neck Cancer (HNC) has improved over recent decades. However, mortality within six months after diagnosis for curative patients remains at approximately 5%. The aim of this study was to identify risk factors for early death among patients with curative treatment, and furthermore, to analyze whether the risk of early death changed over recent years. MATERIAL AND METHOD: This real-world, population-based, nationwide study from the Swedish Head and Neck Cancer Register (SweHNCR) included all patients ≥18 years diagnosed with HNC with a curative treatment intent at the multidisciplinary tumor board from 2008 to 2020. A total of 16,786 patients were included. RESULTS: During the study period a total of 618 (3.7%) patients with curative-intended treatment died within six months of diagnosis. Patients diagnosed between 2008 and 2012 had a six-month mortality rate of 4.7% compared to 2.5% for patients diagnosed between 2017 and 2020, indicating a risk reduction of 53% (p <0.001) for death within six months. The mean time to radiation therapy from diagnosis in the 2008-2012 cohort was 38 days, compared to 22 days for the 2017-2020 cohort, (p <0.001). The mean time to surgery from diagnosis was 22 days in 2008-2012, compared to 15 days for the 2017-2020 cohort, (p <0.001). Females had a 20% lower risk of dying within six months compared to males (p = 0.013). For every year older the patient was at diagnosis, a 4.8% (p <0.001) higher risk of dying within six months was observed. Patients with a WHO score of 1 had approximately 2.4-times greater risk of early death compared to WHO 0 patients (p <0.001). The risk of early death among WHO 4 patients was almost 28 times higher than for WHO 0 patients (p <0.001). Patients with a hypopharyngeal tumor site had a 2.5-fold higher risk of dying within six months from diagnosis compared to oropharyngeal tumor patients (p <0.001). CONCLUSIONS: We found that the risk of early death decreased significantly from 2008 to 2020. During this period, the mean time to the start of treatment was significantly reduced both for surgery and oncological treatment regimes. Among patients with a curative treatment intention, increased risk of early death was associated with male sex, older age, advanced disease, increased WHO score, and a hypopharyngeal tumor site.

Latin American Consensus on the Treatment of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.

Partial recovery of peripheral blood monocyte subsets in head and neck squamous cell carcinoma patients upon radio(chemo)therapy is associated with decreased plasma CXCL11.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) represents a common and heterogeneous malignancy of the oral cavity, pharynx and larynx. Surgery and radio(chemo)therapy are the standard treatment options and also have great influence on the composition of the tumor microenvironment and immune cell functions. However, the impact of radio(chemo)therapy on the distribution and characteristics of circulating monocyte subsets in HNSCC are not fully understood. METHODS: Expression patterns of adhesion molecules and chemokine receptors CD11a (integrin-α L; LFA-1), CD11b (integrin-α M; Mac-1), CD11c (integrin-α X), CX3CR1 (CX3CL1 receptor) and checkpoint molecule PD-L1 (programmed cell death ligand-1) were investigated upon radio(chemo)therapeutic treatment using flow cytometry. Furthermore, comprehensive analysis of plasma cytokines was performed before and after treatment using ELISA measurements. RESULTS: Our data reveal a partial recovery of circulating monocytes in HNSCC patients upon radio(chemo)therapeutic treatment, with differential effects of the individual therapy regimen. PD-L1 expression on non-classical monocytes significantly correlates with the individual plasma levels of chemokine CXCL11 (C-X-C motif chemokine 11). CONCLUSIONS: Further comprehensive investigations on larger patient cohorts are required to elucidate the meaningfulness of peripheral blood monocyte subsets and chemokine CXCL11 as potential bioliquid indicators in HNSCC with regard to therapy response and the individual immunological situation.

Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic stratification.

Head and neck squamous cell carcinoma (HNSCC) is characterized by high recurrence or distant metastases rate and the prognosis is challenging. There is mounting evidence that tumor-infiltrating B cells (TIL-Bs) have a crucial, synergistic role in tumor control. However, little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade. Using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, the study identified distinct gene expression patterns in TIL-Bs. HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering. This classification was further validated with TCGA HNSCC data, correlating with patient prognosis, immune cell infiltration, and response to immunotherapy. We found that the B cells activation group exhibited a better prognosis, higher immune cell infiltration, and distinct immune checkpoint levels, including elevated PD-L1. A prognostic model was also developed and validated, highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients. Overall, this study provides a foundational approach for B cells-based tumor classification in HNSCC, offering insights into targeted treatment and immunotherapy strategies.

Identification of two distinct head and neck squamous cell carcinoma subtypes based on fatty acid metabolism-related signatures: Implications for immunotherapy and chemotherapy.

The dysregulation of lipid metabolism is a critical factor in the initiation and progression of tumors. In this investigation, we aim to characterize the molecular subtypes of head and neck squamous cell carcinoma (HNSCC) based on their association with fatty acid metabolism and develop a prognostic risk model. The transcriptomic and clinical data about HNSCC were obtained from public databases. Clustering analysis was conducted on fatty acid metabolism genes (FAMG) associated with prognosis, utilizing the non-negative matrix factorization algorithm. The immune infiltration, response to immune therapy, and drug sensitivity between molecular subtypes were evaluated. Differential expression genes were identified between subtypes, and a prognostic model was constructed using Cox regression analyses. A nomogram for HNSCC was constructed and evaluated. Thirty FAMGs have been found to exhibit differential expression in HNSCC, out of which three are associated with HNSCC prognosis. By performing clustering analysis on these 3 genes, 2 distinct molecular subtypes of HNSCC were identified that exhibit significant heterogeneity in prognosis, immune landscape, and treatment response. Using a set of 7778 genes that displayed differential expression between the 2 molecular subtypes, a prognostic risk model for HNSCC was constructed comprising 11 genes. This model has the ability to stratify HNSCC patients into high-risk and low-risk groups, which exhibit significant differences in prognosis, immune infiltration, and immune therapy response. Moreover, our data suggest that this risk model is negatively correlated with B cells and most T cells, but positively correlated with macrophages, mast cells, and dendritic cells. Ultimately, we constructed a nomogram incorporating both the risk signature and radiotherapy, which has demonstrated exceptional performance in predicting prognosis for HNSCC patients. A molecular classification system and prognostic risk models were developed for HNSCC based on FAMGs. This study revealed the potential involvement of FAMGs in modulating tumor immune microenvironment and response to treatment.