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This retrospective study analyzed the efficacy of PD-1 inhibitors combined with albumin-bound paclitaxel and cisplatin (TP regimen) in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma (RMHSCC/RMLSCC). Patients diagnosed and treated at the Sun Yat-sen University Cancer Center from August 1, 2020, to August 15, 2023, with histologically confirmed RMHSCC/RMLSCC were included. All patients received PD-1 inhibitors combined with albumin-bound paclitaxel (260mg/m2) and cisplatin (60mg/m2) for 3-4 cycles. The primary endpoints were overall survival (OS) and progression-free survival (PFS). A total of 50 patients with RMHSCC/RMLSCC who received TP+PD-1 inhibitor therapy were included, with an objective response rate (ORR) of 56.0% (28/50). The 1-year and 2-year OS rates were 80.2% (95% CI: 69.3%-92.9%) and 68.6% (95% CI: 52.6%-89.5%), respectively, while the 1-year and 2-year PFS rates were 44.7% (95% CI: 31.9%-62.5%) and 26.0% (95% CI: 12.6%-53.4%), respectively. Treatment-related adverse events mainly included rash, myelosuppression, gastrointestinal reactions, and hypothyroidism. In the treatment of RMHSCC/RMLSCC with TP + PD-1 inhibitors, survival rates of patients can be improved while ensuring the safety of the treatment regimen.

Laryngeal cancer has the second highest incidence of head and neck malignant tumors worldwide. In recent years, studies have shown that human papillomavirus (HPV) infection may be a high-risk factor for laryngeal cancer and closely related to the development and prognosis of laryngeal cancer. The mechanism of the occurrence and development of laryngeal cancer caused by HPV infection needs investigation, as does a rapid and effective HPV detection method for effectively preventing the occurrence of laryngeal cancer and controlling its development. Many studies have explored the relation between HPV infection and laryngeal cancer. Here we review the research progress in investigating HPV infection in terms of DNA, mRNA and protein levels in the occurrence and development of laryngeal cancer and routine HPV detection methods.

Background: Cervical lymph nodes metastases are one of the most significant prognostic factors in patients with laryngeal carcinoma, whether treatment by surgery or by radiotherapy. The current study retrospected the postoperative radiotherapy of locally advanced supraglottic and glottic laryngeal carcinoma (at a greater risk of lymph node metastasis) to determine the effect of radiotherapy excluding cervical level Ⅳ lymph nodes. Methods: Patients of supraglottic type and glottic type were irradiated with level Ⅳ from January 2012 to June 2013, without level Ⅳ from July 2013 to December 2014, according to physicians’ decision. Ninety-three patients were selective neck irradiation (SNI) of levels Ⅱ-Ⅳ (Group A) and 87 patients were SNI of levels Ⅱ and Ⅲ (Group B). The comparison between Group A and Group B was made with observation of clinical risk of recurrence and radiation complications, as well as overall survival (OS), progress-free survival (PFS) and regional nodal recurrence-free survival. Results: No remarkable difference was observed in the distribution of recurrence, levels of relapse, OS, PFS and regional nodal recurrence-free survival between the 2 groups (p > 0.05). Mean radiation dose at level Ⅳ, thyroid and cervical esophagus showed significant difference between the 2 therapeutic groups (p < 0.01). As regard radiation complications, no significant difference was found in radiation dermatitis of any grade between the 2 groups (p > 0.05). However, there was remarkable difference in clinical hypothyroidism and radiation esophagitis between Group A and Group B (p < 0.05). Conclusions: Radiotherapy after surgery omitting level Ⅳ may improve the quality of life in patients with locally advanced supraglottic and glottic laryngeal carcinoma, won’t worsen the prognosis as well.

The accurate preoperative staging of laryngeal squamous cell carcinoma (LSCC) provides valuable guidance for clinical decision-making. The objective of this study was to establish a multiparametric MRI model using radiomics and deep learning (DL) to preoperatively distinguish between Stages I–II and III–IV of LSCC. Data from 401 histologically confirmed LSCC patients were collected from two centers (training set: 213; internal test set: 91; external test set: 97). Radiomics features were extracted from the MRI images, and seven radiomics models based on single and combined sequences were developed via random forest (RF). A DL model was constructed via ResNet 18, where DL features were extracted from its final fully connected layer. These features were fused with crucial radiomics features to create a combined model. The performance of the models was assessed using the area under the receiver operating characteristic (ROC) curve (AUC) and compared with the radiologist performances. The predictive capability of the combined model for Progression-Free Survival (PFS) was evaluated via Kaplan–Meier survival analysis and the Harrell’s Concordance Index (C-index). In the external test set, the combined model had an AUC of 0.877 (95% CI 0.807–0.946), outperforming the DL model (AUC: 0.811) and the optimal radiomics model (AUC: 0.835). The combined model significantly outperformed both the DL ( p  = 0.017) and the optimal radiomics models ( p  = 0.039), and the radiologists (both p  < 0.050). Moreover, the combined model demonstrated great prognostic predictive value in patients with LSCC, achieving a C-index of 0.624 for PFS. This combined model enhances preoperative LSCC staging, aiding in making more informed clinical decisions.

Immunoscore (IS), based on CD3/CD8, has been proposed to characterize the immune landscape of the tumor immune microenvironment and has demonstrated an association with the prognosis of laryngeal squamous cell carcinoma (LSCC). However, traditional IS does not include immunosuppressive cells. The purpose of this study is to evaluate the prognostic performance of cytotoxic-T-lymphocytes to immunosuppressive cells ratio (CIL) in laryngeal squamous cell carcinoma (LSCC) patients. Two cohorts were included in this study: The training cohort ( N  = 75) consisted of tumor tissue microarrays from LSCC patients in our department, and the validation cohort ( N  = 116) utilized bulk RNA-seq data from the TCGA database. Patients with high IS or CIL showed significantly prolonged overall survival and disease-free survival in both cohorts. Upon analyzing the relative contribution of each parameter, it was found that CIL exhibited the highest significance among the factors examined. It emerged as the strongest predictor of overall survival, emphasizing its crucial influence in determining the outcomes. The prognostic ability of IS-TCGA was similar to the original IS. Additionally, high CILM2-TCGA was associated with prolonged survival of patients with LSCC in the TCGA dataset. CIL, which is easier to construct than IS, proves to be reliable in predicting survival outcomes for patients with LSCC.

Background Laryngeal squamous cell carcinoma (LSCC) is the most common type of head and neck malignancy. NAT10 is a catalytic enzyme for ac4C and is involved in the progression of a variety of cancers. This study aimed to explore the effects and potential mechanisms of NAT10 in LSCC. Methods Pyroptosis was assessed by measuring the release of lactic dehydrogenase, pyroptosis rate, and pyroptosis-related proteins. The RNA and protein levels were detected by quantitative real-time PCR and western blot, respectively. Potential mechanisms were validated using flow cytometry, ac4C dot blot, methylated RNA immunoprecipitation (MeRIP), RIP, and Dual-Luciferase Reporter Assay experiments. Results The result showed that the levels of NAT10 in LSCC tissues and cells were elevated and positively correlated with tumor grading and clinical staging. Knockdown of NAT10 promoted the pyroptosis of LSCC cells. NAT10 directly interacted with ELANE, suppressed the stability of the ELANE mRNA. NAT10 inhibited pyroptosis in LSCC by downregulating the ELANE expression in vivo and in vitro. Conclusion NAT10 inhibited the pyroptosis of LSCC cells and contributed to LSCC progression by suppressing ELANE mRNA stability in ac4C modification manner, indicating that the NAT10-ac4C-ELANE axis might be a potential target for LSCC.

BackgroundThis study aimed at exploring high-risk factors associated with survival outcomes in patients with advanced primary laryngeal carcinoma and at developing and validating a survival-predicting model to help to select the appropriate treatment for each patient.MethodsData of patients with advanced primary laryngeal cancer in 2003–2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. High-risk factors were identified and integrated to build a nomogram, which was internally validated using bootstrap and externally validated with a patient cohort from China. The impact of various treatments was examined on model-defined high-, moderate- and low-risk patient groups, respectively.ResultsA total of 6070 patients were analyzed. Patients’ age, gender, tumor T stage, N stage, and differentiation grade were recognized and integrated into the model. The concordance index of this model (0.602) was significantly higher than that of the TNM staging system (0.547). The calibration curve showed a good agreement between model-predicted and actual survival outcomes. Patients were categorized into three different subgroups with incremental risks of overall mortality. The roles of three treatment strategies in these subgroups are varied.ConclusionIn this large SEER-based study, we established a practical model to predict overall survival for patients with advanced primary laryngeal cancer. For patients identified as high-risk and moderate-risk, surgery plus adjuvant therapy is recommended, while for patients in the low-risk group, surgery alone plus regular re-examination is recommended as the primary treatment strategy.

BackgroundHHLA2 (human endogenous retrovirus-H long terminal repeat-associating protein 2) represents a recently identified member of the B7 immune checkpoint family, characterized by limited expression in normal tissues but notable overexpression in various cancer types. Nevertheless, the precise function and interaction with immune cells remain poorly understood, particularly in laryngeal squamous cell carcinoma (LSCC). This investigation endeavored to elucidate the biological significance of HHLA2 within the tumor microenvironment of human LSCC tissues and delineate the clinical relevance and functional roles of HHLA2 in LSCC pathogenesis.MethodsThrough multiplexed immunohistochemistry analyses conducted on tissue microarrays sourced from LSCC patients (n = 72), the analysis was executed to assess the expression levels of HHLA2, density and spatial patterns of CD68+HLA-DR+CD163− (M1 macrophages), CTLA-4+CD4+FoxP3+ (CTLA-4+Treg cells), CTLA-4+CD4+FoxP3− (CTLA-4+Tcon cells), exhausted CD8+T cells, and terminally exhausted CD8+T cells in LSCC tissues. Survival analysis was conducted to evaluate the prognostic significance of HHLA2 and these immune checkpoints or immune cell populations, employing COX regression analysis to identify independent prognostic factors.ResultsKaplan–Meier (K–M) survival curves revealed a significant association between HHLA2 expression and overall survival (OS) in LSCC. Elevated levels of HHLA2 were linked to reduced patient survival, indicating its potential as a prognostic marker (HR: 3.230, 95%CI 0.9205–11.34, P = 0.0067). Notably, increased infiltration of CD68+ cells (total macrophages), STING+CD68+HLA-DR+CD163− (STING+M1 macrophages), CTLA-4+CD4+FoxP3+, CTLA-4+CD4+FoxP3−, PD-1+LAG-3+CD8+T cells, and PD-1+LAG-3+TIM-3+CD8+T cells strongly linked to poorer survival outcomes (P < 0.05). A discernible trend was observed between the levels of these immune cell populations, STING+CD68+ (STING+ total macrophages), CD68+HLA-DR+CD163−, STING+CD68+CD163+HLA-DR− (STING+M2 macrophages), PD-1+LAG-3−CD8+T cells, PD-1+TIM-3+CD8+T cells, and PD-1+LAG-3+TIM-3−CD8+T cells and prognosis. Importantly, multivariate COX analysis identified HHLA2 as an independent predictive factor for OS in LSCC patients (HR = 3.86, 95%CI 1.08–13.80, P = 0.038). This underscored the potential of HHLA2 as a critical marker for predicting patient outcomes in LSCC.ConclusionsHHLA2 emerged as a detrimental prognostic biomarker for assessing OS in LSCC patients. Relative to other immune checkpoints, HHLA2 exhibited heightened predictive efficacy for the prognosis of LSCC patients.

The lncRNA NEAT1 has been shown to promote the progression of several cancers, containing laryngeal squamous cell carcinoma (LSCC). However, the precise mechanism by which it promotes LSCC progression remains unclear. In this study, we verified the high expression of lncRNA NEAT1 in LSCC tissues and cells using RT-qPCR. Analysis of clinical data exhibited that high expression of lncRNA NEAT1 was associated with a history of smoking, worse T stage, lymph node metastasis, and later TNM stage in patients with LSCC. The promotion effect of lncRNA NEAT1 on LSCC cell proliferation, migration, invasion, and tumor growth in vivo was verified by CCK-8, plate clone formation, Transwell, and nude mouse tumorigenicity assays. Bioinformatics prediction and double luciferase reporter gene assay verified the binding of miR-411-3p to lncRNA NEAT1 and FZD3 mRNA, and inhibition of miR-411-3p reversed the inhibitory effect of lncRNA NEAT1 on FZD3 expression in LSCC cells. We also verified that lncRNA NEAT1-mediated FZD3 activation in the Wnt pathway affects LSCC development. In conclusion, we demonstrate that lncRNA NEAT1 promotes the progression of LSCC, and propose that the lncRNA NEAT1/miR-411-3p/FZD3 axis may be an effective target for LSCC therapy.

Background Tumor-derived small extracellular vesicles (sEVs) play an essential role in reprogramming the tumor microenvironment. Metabolic reprogramming is an essential prerequisite for M2 polarization of tumor-associated macrophages (TAMs). This M2 phenotype is closely related to the immune dysfunction of CD8 + T cells and subsequent tumor progression. This study evaluates the role of laryngeal squamous cell carcinoma cell-derived small extracellular vesicles (LSCC-sEVs) in M2 polarization of TAMs and CD8 + T cell dysfunction, and delineates the underlying mechanisms. Methods Human leukemia monocyte cell line (THP-1) was induced to differentiate into M0 macrophages using phorbol 12-myristate 13-acetate. M0 macrophages were incubated with sEVs derived from LSCC cells TU212. CD8 + T cells, extracted from peripheral blood mononuclear cells of healthy volunteer donors, were co-cultured with the LSCC-sEV-treated M0 macrophages to evaluate their proliferation, and immune function. The role of LSCC-sEVs was investigated in macrophage tumor-bearing mouse models. Results LSCC-sEVs promoted TAM M2 polarization and impaired CD8 + T cell function, attributing to PD-L1 expression upregulation. In addition, suppression of metabolic reprogramming could partially reverse LSCC-sEV-induced CD8 + T cell dysfunction. STC-1 was found highly enriched in LSCC-sEVs. Knockdown of STC1 abrogated metabolic reprogramming of TAMs into M2-like macrophages and restored CD8 + T cell function. Importantly, in vivo results showed that LSCC-sEVs transform TAMs into M2 phenotype by mediating metabolic reprogramming and induce CD8 + T cell dysfunction, ultimately accelerating tumor growth. Conclusion Our data reveal a previously undescribed role for LSCC-sEVs in the regulation of M2 polarization of TAMs and immune cell function through STC1 mediated metabolic reprogramming.