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    Current role of computed tomography imaging in the evaluation of cartilage invasion by laryngeal carcinoma. Pietragalla Michele,Nardi Cosimo,Bonasera Luigi,Mungai Francesco,Verrone Giovanni Battista,Calistri Linda,Taverna Cecilia,Novelli Luca,Locatello Luca Giovanni,Mannelli Giuditta,Gallo Oreste,Miele Vittorio La Radiologia medica OBJECTIVES:To evaluate thyroid, arytenoid, and cricoid cartilage invasion on computed tomography (CT) imaging in patients undergoing total laryngectomy for both primary and recurrent laryngeal carcinoma. Secondary endpoint was to compare laryngeal cartilage invasion between primary and recurrent tumours. METHODS:Pre-treatment CT of 40 patients who had undergone total laryngectomy was retrospectively evaluated and compared with histology. Focal erosions of thyroid cartilage were accounted for neoplastic invasion of the inner cortex. Full-thickness thyroid cartilage invasion was defined as a tumour-like tissue replacing thyroid cartilage or extended in extra-laryngeal soft tissues. Sclerosis and erosion of arytenoid and cricoid cartilages were assessed as signs of neoplastic invasion. RESULTS:CT erosion showed perfect agreement for thyroid inner cortex and cricoid cartilage invasion and almost perfect agreement (87%) for arytenoid cartilage invasion. For tumours in contact with thyroid cartilages, the absence of CT erosion underestimated inner cortex infiltration. CT showed perfect agreement in predicting full-thickness thyroid cartilage invasion only in the case of extra-laryngeal neoplastic extension. Arytenoid sclerosis showed poor correlation with neoplastic invasion. For primary tumours, CT demonstrated good (inner cortex 75%; full-thickness 85%), substantial (67.5%), and perfect (100%) accuracy in thyroid, arytenoid, and cricoid cartilage invasion, respectively. No CT differences were observed between primary and recurrent laryngeal tumours. CONCLUSION:Tumour-like tissue extension in the extra-laryngeal soft tissues was accurate in predicting thyroid cartilage full-thickness invasion. Erosions of arytenoid, cricoid, and thyroid cartilages' inner cortex on CT were highly indicative of neoplastic infiltration. No CT difference in cartilage infiltration between primary and recurrent tumours was observed. 10.1007/s11547-020-01213-y
    Profiles of immune cell infiltration in head and neck squamous carcinoma. Liang Bin,Tao Ye,Wang Tianjiao Bioscience reports Tumor immune infiltration cells (TIICs) are highly heterogeneous, not only in different cancer subtypes but also within different cancer regions. We conducted the Cell-type Identification using Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) method. We assessed the relative proportions of 22 TIICs in HNSC using publicly available TCGA transcriptional datasets, analyzed the proportions of TIICs between HNSC tissues and normal tissues, along with accompanying clinicopathological data, and the impact of TIICs on clinical outcome. After the filter criteria, a total of 395 patients were included in the analysis. We found significant differences in naïve B cells, monocytes, resting mast cells, activated mast cells, CD8+ T cells, and M0 macrophages between HNSC tissues and adjacent non-cancer tissues. We also found that some TIIC subgroups were significantly associated with clinical parameters. Moreover, the patients with low Tregs fraction had worse OS and DFS than those with high Tregs fraction. However, low M0 macrophages fraction was associated with better OS and DFS in HNSC patients. Moreover, Tregs and M0 macrophages are likely to be important determinants of prognosis, which may serve as a potential immunotherapy target for HNSC. Then, we screened the immune-related differentially expressed genes (DEGs), performed the GO and KEGG enrichment analysis, constructed the protein-protein interaction network, and screened the prognosis-related hub genes in HNSC. However, further clinical investigation and basic experiments are needed to validate our results, and uncover the molecular mechanisms interlinking TIICs in HNSC and their roles in prognosis and therapy. 10.1042/BSR20192724
    The prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma: A gene expression-based study. Zhang Lizao,Li Bowen,Peng Yu,Wu Fan,Li Qunxing,Lin Zhaoyu,Xie Shule,Xiao Liping,Lin Xinyu,Ou Zhanpeng,Cai Tingting,Rong Haixu,Fan Song,Li Jinsong Oral oncology OBJECTIVE:Whether tumor mutation burden (TMB) affects prognosis and immune infiltration of tumor patients is controversial. We designed and conducted a multi-omics study with the aim of investigating the prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma (HNSCC). METHODS:TMB scores were calculated from the mutation data of 506 HNSCC samples from The Cancer Genome Atlas (TCGA), and the patients were divided into low- and high-TMB groups according to the TMB score quartiles. Differentially expressed genes (DEGs) between the low-TMB and high-TMB groups were identified. Immune cell infiltration and survival analyses were conducted between groups. RESULTS:High TMB in HNSCC patients was associated with a poor prognosis, large primary tumor size, advanced clinical stage and a human papillomavirus (HPV)-negative status. A total of 576 DEGs were identified, and gene set enrichment analysis (GSEA) revealed that the DEGs in the low-TMB group were enriched in immune-related pathways. Four hub genes were significantly associated with prognosis, and mutations in these genes affected immune infiltration. The estimated fractions of B memory cells and CD4+ memory resting cells were higher in the low-TMB group than in the high-TMB group, and B cell and CD4+T cell infiltration was positively correlated with prognosis in HNSCC patients. CONCLUSIONS:HNSCC patients with low TMB have better prognoses than those with high TMB, and TMB might affect B cell and CD4+T cell infiltration. 10.1016/j.oraloncology.2020.104943
    Prognostic role of programmed death ligand 1 (PD-L1) and the immune microenvironment in laryngeal carcinoma. Alessandrini Lara,Franz Leonardo,Ottaviano Giancarlo,Ghi Maria Grazia,Lanza Cristiano,Blandamura Stella,Marioni Gino Oral oncology OBJECTIVES:The immune system is crucial in the evolution of head and neck cancer. Programmed cell death ligand 1 (PD-L1) seems to rely on close relations between neoplastic cells and immune cells in the tumor microenvironment. The main aim of this study was to apply univariate/multivariate analysis to investigate the prognostic significance of PD-L1, tumor-infiltrating lymphocytes (TILs), and tertiary lymphoid structures (TLS) in laryngeal carcinoma (LSCC). MATERIALS AND METHODS:PD-L1 (in terms of combined positive score [CPS]), TILs and TLS were assessed at pathology on 70 consecutive samples of LSCC. RESULTS:A CPS ≥ 1 coincided with a lower recurrence rate (RR) (p = 0.007) and longer disease-free survival (DFS) than a CPS < 1 (p = 0.0027). Cases with higher TIL counts showed a lower RR (p = 0.036) and longer DFS than those with lower TIL counts (p = 0.0062). Cases revealing TLS had a lower RR (p = 0.004) and longer DFS (p = 0.0034) than those with no TLS. On multivariate analysis, the presence of TLS retained its positive prognostic value (p = 0.024), while CPS remained significant as regards disease recurrence (p = 0.050). CONCLUSIONS:PD-L1 seems to be an indirect marker of effective anti-tumor response in LSCC, possibly being expressed as a result of a greater immune pressure on cancer cells. The presence of TLS emerged as a positive prognostic factor. Further prospective studies are needed to characterize the role of PD-L1 as a marker of anti-tumor immune response and prognostic factor in LSCC, also with regard to the effectiveness of immunotherapeutic protocols. 10.1016/j.oraloncology.2020.104836
    Profiles of immune cell infiltration and their clinical significance in head and neck squamous cell carcinoma. Jin Yu,Qin Xing International immunopharmacology It is well established that there exist comprehensive interactions between tumor immunology and tumor biology. Tumor-infiltrating immune cells (TIICs) have been appealing therapeutic targets due to their significance in regulating cancer progression. The purpose of this study was to illustrate the comprehensive landscape of TIICs composition in head and neck squamous cell carcinoma (HNSCC) and their clinical significance. CIBERSORT was applied to calculate the 22 immune cell types proportion in HNSCC and further analysis suggested that six kinds of immune cells (resting memory CD4 T cells, M1 macrophages, resting dendritic cells, resting mast cells, monocytes, and eosinophils) were closely correlated with HNSCC progression. Moreover, memory CD4 T cells may serve as prognosis indicator for HNSCC patients. Collectively, this study uncovered the immune cells infiltration landscape in HNSCC and illustrated their potential relationships with clinical parameters, thereby contributing to the development of customized treatment strategy. 10.1016/j.intimp.2020.106364
    Comprehensive analysis of significant genes and immune cell infiltration in HPV-related head and neck squamous cell carcinoma. Xu Lei,Jin Yu,Qin Xing International immunopharmacology Head and neck squamous cell carcinoma (HNSCC) is malignancy which impairs the life quality of patients and seriously threatens human life. HPV infection has increasingly been recognized as a significant etiology for HNSCC initiation and progression. Emerging evidences have suggested that HPV+and HPV- HNSCC patients showed different responses to cancer therapy, which may be attributed to varied immune cell infiltration in tumor microenvironment. In the present study, we made a comprehensive analysis of significant genes and immune cell infiltration in HNSCC with different HPV status. Firstly, transcriptome data of HNSCC samples with available HPV status was downloaded from The Gene Expression Omnibus (GEO) database and differential expression analysis was performed. A total of 61 differentially expressed genes (DEGs) including 32 upregulated and 29 downregulated genes were identified in HPV+ HNSCC when compared to HPV- HNSCC. Further enrichment analysis demonstrated these DEGs were closely associated with cancer-related biological functions and signaling pathways. Infiltration of 22 kinds of immune cells was evaluated by CIBERSORT based on gene expression matrix. As a result, it was indicated that the infiltration of follicular helper T cells, gamma delta T cells, monocytes, eosinophils and neutrophils presented significantly differences between HPV+ and HPV- HNSCC. Collectively, our findings may provide new evidences for the development of immunotherapy and personalized precision medicine for HNSCC with different HPV status. 10.1016/j.intimp.2020.106844
    Female Gender Predicts Augmented Immune Infiltration in Lung Adenocarcinoma. Behrens Carmen,Rocha Pedro,Parra Edwin R,Feng Lei,Rodriguez-Canales Jaime,Solis Luisa M,Mino Barbara,Zhang Jianjun,Gibbons Don L,Sepesi Boris,Rice David,Heymach John V,Moran Cesar,Creighton Chad J,Lee J Jack,Kadara Humam,Wistuba Ignacio I Clinical lung cancer INTRODUCTION:Immune infiltration in lung adenocarcinomas (LUADs) has been associated with response to immune checkpoint inhibitors. Clinical features underlying differential responses of patients with LUADs to immunotherapy are not well understood. Here, we analyzed the association between LUAD immune infiltration and clinicopathologic variables. MATERIALS AND METHODS:Intratumoral CD3, CD8, and CD68 cell densities (tumor-associated immune cells [TAICs]) were immunohistochemically assessed in 146 surgically resected LUADs. LUADs were classified into 2 groups, low and high TAICs, based on the median values of cell densities for CD3, CD8, and CD68. Somatic mutation burden and driver gene mutation status were analyzed in a subset of the cases (n = 92). We statistically analyzed the association between the TAIC groups and various clinicopathologic and molecular variables by using the χ/Fisher and Wilcoxon sum tests and multivariable logistic regression models. RESULTS:Patient gender, tumor size, and STK11 mutations were significantly associated with TAIC levels in LUAD. Female patients exhibited significantly elevated TAIC levels (P = .005) compared with male patients. Tumor size was inversely associated with TAIC levels (P = .012). STK11 mutated tumors were associated with lower TAICs (P = .008). Higher TAICs were consistently observed in female patients with LUADs after adjusting for stage, tumor size, and age. Multivariable regression models confirmed female gender as an independent variable associated with TAIC levels in LUAD (P = .0141). CONCLUSION:Immune infiltration in LUADs was significantly higher in female patients, warranting further exploration into the association between this clinical variable and immunotherapeutic response in LUAD. 10.1016/j.cllc.2020.06.003