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1.
Int J Surg ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38729119

ABSTRACT

INTRODUCTION: The incidence of occult cervical lymph node metastases (OCLNM) is reported to be 20%-30% in early-stage oral cancer and oropharyngeal cancer. There is a lack of an accurate diagnostic method to predict occult lymph node metastasis and to help surgeons make precise treatment decisions. AIM: To construct and evaluate a preoperative diagnostic method to predict occult lymph node metastasis (OCLNM) in early-stage oral and oropharyngeal squamous cell carcinoma (OC and OP SCC) based on deep learning features (DLFs) and radiomics features. METHODS: A total of 319 patients diagnosed with early-stage OC or OP SCC were retrospectively enrolled and divided into training, test and external validation sets. Traditional radiomics features and DLFs were extracted from their MRI images. The least absolute shrinkage and selection operator (LASSO) analysis was employed to identify the most valuable features. Prediction models for OCLNM were developed using radiomics features and DLFs. The effectiveness of the models and their clinical applicability were evaluated using the area under the curve (AUC), decision curve analysis (DCA) and survival analysis. RESULTS: Seventeen prediction models were constructed. The Resnet50 deep learning (DL) model based on the combination of radiomics and DL features achieves the optimal performance, with AUC values of 0.928 (95% CI: 0.881-0.975), 0.878 (95% CI: 0.766-0.990), 0.796 (95% CI: 0.666-0.927) and 0.834 (95% CI: 0.721-0.947) in the training, test, external validation set1 and external validation set2, respectively. Moreover, the Resnet50 model has great prediction value of prognosis in patients with early-stage OC and OP SCC. CONCLUSION: The proposed MRI-based Resnet50 deep learning model demonstrated high capability in diagnosis of OCLNM and prognosis prediction in the early-stage OC and OP SCC. The Resnet50 model could help refine the clinical diagnosis and treatment of the early-stage OC and OP SCC.

2.
J Transl Med ; 22(1): 477, 2024 May 19.
Article in English | MEDLINE | ID: mdl-38764038

ABSTRACT

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a malignant tumor with a poor prognosis. Traditional treatments have limited effectiveness. Regulation of the immune response represents a promising new approach for OSCC treatment. B cells are among the most abundant immune cells in OSCC. However, the role of B cells in OSCC treatment has not been fully elucidated. METHODS: Single-cell RNA sequencing analysis of 13 tissues and 8 adjacent normal tissues from OSCC patients was performed to explore differences in B-cell gene expression between OSCC tissues and normal tissues. We further investigated the relationship between differentially expressed genes and the immune response to OSCC. We utilized tissue microarray data for 146 OSCC clinical samples and RNA sequencing data of 359 OSCC samples from The Cancer Genome Atlas (TCGA) to investigate the role of T-cell leukemia 1 A (TCL1A) in OSCC prognosis. Multiplex immunohistochemistry (mIHC) was employed to investigate the spatial distribution of TCL1A in OSCC tissues. We then investigated the effect of TCL1A on B-cell proliferation and trogocytosis. Finally, lentiviral transduction was performed to induce TCL1A overexpression in B lymphoblastoid cell lines (BLCLs) to verify the function of TCL1A. RESULTS: Our findings revealed that TCL1A was predominantly expressed in B cells and was associated with a better prognosis in OSCC patients. Additionally, we found that TCL1A-expressing B cells are located at the periphery of lymphatic follicles and are associated with tertiary lymphoid structures (TLS) formation in OSCC. Mechanistically, upregulation of TCL1A promoted the trogocytosis of B cells on dendritic cells by mediating the upregulation of CR2, thereby improving antigen-presenting ability. Moreover, the upregulation of TCL1A expression promoted the proliferation of B cells. CONCLUSION: This study revealed the role of B-cell TCL1A expression in TLS formation and its effect on OSCC prognosis. These findings highlight TCL1A as a novel target for OSCC immunotherapy.


Subject(s)
B-Lymphocytes , Carcinoma, Squamous Cell , Gene Expression Regulation, Neoplastic , Mouth Neoplasms , Proto-Oncogene Proteins , Tertiary Lymphoid Structures , Humans , Prognosis , Mouth Neoplasms/pathology , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Mouth Neoplasms/immunology , Tertiary Lymphoid Structures/pathology , Tertiary Lymphoid Structures/immunology , Tertiary Lymphoid Structures/metabolism , B-Lymphocytes/metabolism , B-Lymphocytes/immunology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/metabolism , Female , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , Male , Middle Aged , Cell Line, Tumor , Cell Proliferation
3.
BMC Oral Health ; 24(1): 32, 2024 01 06.
Article in English | MEDLINE | ID: mdl-38184544

ABSTRACT

BACKGROUND: The neck management of clinical-nodal negative (cN0) oral squamous cell carcinoma (OSCC) remains controversial. Elective neck dissection (END) and observation are the main strategies, but it is still not clear who could benefit the most from END. The purpose of this study was to clarify the potential clinical factors that affect the therapeutic value of END and to explore the actual characteristics associated with benefit from END. METHODS: Patients with cN0 OSCC were identified in the SEER database from 2000 to 2019. 5-year Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan‒Meier method, and the hazard ratios (HRs) for survival were estimated using the Cox regression model. Multiple subgroup analyses of DSS and OS among different factors, comparing END and No END, were performed. RESULTS: A total of 17,019 patients with cN0 OSCC were included. The basic survival analysis and Cox regression model showed that END increased the probability of 5-year DSS and OS and was an independent prognostic factor. However, among patients who underwent only primary tumor surgery, no significant differences were found between the END and No END groups in 5-year DSS (P = 0. 585) and OS (P = 0.465). Further subgroup analysis showed that primary sites and T stage, but not other factors, might influence the benefit of END. Significant differences were found for T1 (P < 0.001 for OS) and T2 (P = 0.001 for DSS and < 0.001 for OS) tongue squamous cell carcinoma (TSCC) but not for other primary tumor sites. CONCLUSION: This large-scale retrospective population-based cohort study suggests that not all patients with cN0 OSCC could benefit from END. Patients with cN0 TSCC are recommended to undergo END, especially with early-stage tumors.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Tongue Neoplasms , Humans , Carcinoma, Squamous Cell/surgery , Squamous Cell Carcinoma of Head and Neck , Neck Dissection , Mouth Neoplasms/surgery , Cohort Studies , Retrospective Studies
4.
Head Neck ; 46(3): 528-540, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38111234

ABSTRACT

BACKGROUND: We aimed to unbiasedly map the genetic mutation profile of HNSC and CESC associated with HPV status in the Chinese population (SYSU-cohort) and compare them with Western population (TCGA-cohort). METHODS: Fifty-one HNSC patients (SYSU-HNSC) and 38 CESC patients (SYSU-CESC) were enrolled in this study. Genomic alterations were examined, and the profile was produced using the YuanSuTM450 gene panel (OrigiMed, Shanghai, China). The altered genes were inferred and compared to Western patients from TCGA cohorts. RESULTS: Compared to the TCGA-HNSC cohort, FGFR3 mutation was identified as a novel target in SYSU-HNSC with therapeutic potential. Compared to the TCGA-CESC cohort, some epigenetic regulation-associated genes were frequently mutated in SYSU-CESC cohort (KMT2C, KMT2D, KDM5C, KMT2A). CONCLUSION: In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.


Subject(s)
Head and Neck Neoplasms , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/genetics , Epigenesis, Genetic , China , Head and Neck Neoplasms/genetics , Mutation
5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-964429

ABSTRACT

@#With the development of computer-aided surgery and rapid prototyping via 3D printing technology, digital surgery has rapidly advanced in clinical practice, especially in the field of oral and maxillofacial surgery. 3D printing technology has been applied to the functional restoration and reconstruction of the jawbone. Before surgery, a 3D digital model is constructed through software to plan the scope of the osteotomy, shape the bone graft and plan the placement of the implant. Additionally, 3D models of personalized surgical instrument guides are printed prior to surgery. With these 3D-printed models and guides, accurate excision of the jaw tumor, accurate placement of the grafted bone and precise placement of implants can be achieved during surgery. Postoperative evaluation of accuracy and function shows that 3D printing technology can aid in achieving the biomechanical goals of simultaneous implant placement in jaw reconstruction, and in combination with dental implant restoration, the technology can improve patients' postoperative occlusal and masticatory functions. Nevertheless, 3D printing technology still has limitations, such as time-consuming preparation before surgery. In the future, further development of 3D printing technology, optimization of surgical plans, and alternative biological materials are needed. Based on domestic and foreign literature and our research results, we have reviewed the process and clinical application prospects of jaw reconstruction via 3D printing technology to provide a reference for oral and maxillofacial surgeons.

6.
Nat Commun ; 13(1): 3882, 2022 07 06.
Article in English | MEDLINE | ID: mdl-35794100

ABSTRACT

Mitochondrial dynamics can regulate Major Histocompatibility Complex (MHC)-I antigen expression by cancer cells and their immunogenicity in mice and in patients with malignancies. A crucial role in the mitochondrial fragmentation connection with immunogenicity is played by the IRE1α-XBP-1s axis. XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Mitochondrial fission inhibition with Mdivi-1 upregulates MHC-I expression on cancer cells and enhances the efficacy of adoptive T cell therapy in patient-derived tumor models. Therefore mitochondrial fission inhibition might provide an approach to enhance the efficacy of T cell-based immunotherapy.


Subject(s)
Mitochondrial Dynamics , Neoplasms , Animals , Endoribonucleases , Major Histocompatibility Complex , Mice , Mitochondrial Dynamics/physiology , Neoplasms/therapy , Protein Serine-Threonine Kinases
8.
Ann Plast Surg ; 89(1): 59-62, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35502975

ABSTRACT

OBJECTIVE: Tai Chi is an ancient philosophy used to explain the universe. The Tai Chi symbol is represented by Yin/Yang fishes. The authors describe a novel radial forearm flap (RFF) design for the reconstruction of circular defects based on the Tai Chi symbol. METHODS: Eleven consecutive patients with craniofacial skin or mucus defects underwent reconstruction with a Tai Chi RFF. Patient perioperative and follow-up information was collected. RESULTS: The diameter of the Tai Chi RFF was 5 to 6 cm. All flaps healed uneventfully without ischemic problems, and all donor site defects were closed primarily without skin grafts. Remarkably, 2 patients received a tattoo to mark the Tai Chi symbol and greatly appreciate the shape of the flap. CONCLUSIONS: The Tai Chi flap is an economically friendly flap design that can be used to prevent skin grafts while providing psychological comfort to patients.


Subject(s)
Plastic Surgery Procedures , Tai Ji , Forearm/surgery , Humans , Skin Transplantation , Surgical Flaps/surgery
9.
Medicine (Baltimore) ; 101(17): e28985, 2022 Apr 29.
Article in English | MEDLINE | ID: mdl-35512064

ABSTRACT

BACKGROUND: Cardiogenic shock (CS) is the most serious complication of acute myocardial infarction (AMI) with high mortality, and the conventional nursing mode can not meet the clinical needs. Studies have shown that integrated care model has advantages for critical and chronic diseases. However, there is no clinical study to evaluate the clinical efficacy of this nursing model on cardiogenic shock induced by acute myocardial infarction (CS-AMI). METHODS: This is a prospective randomized controlled trial to study the clinical efficacy of integrated care combined with vasopressin in the treatment of CS-AMI. Participants will be randomized in a 1:1 ratio to receive integrated care combined with vasopressin in the treatment group and conventional care combined with vasopressin in the control group. The patients will be followed up for 3 months after systematic treatment. Observation indicators include: length of hospital stay, quality of life score, blood pressure level, and nursing satisfaction score. Finally, SPASS 20.0 software will be used for statistical analysis of the data. DISCUSSION: This study will evaluate the clinical efficacy of integrated nursing combined with vasopressin in the treatment of CS-AMI. The results of this study will provide a reference for selecting appropriate nursing programs for CS-AMI patients. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/K8CN4.


Subject(s)
Delivery of Health Care, Integrated , Myocardial Infarction , Humans , Prospective Studies , Quality of Life , Randomized Controlled Trials as Topic , Shock, Cardiogenic/etiology , Shock, Cardiogenic/therapy , Treatment Outcome , Vasopressins/therapeutic use
10.
Front Immunol ; 13: 822004, 2022.
Article in English | MEDLINE | ID: mdl-35432345

ABSTRACT

Background: Chimeric antigen receptor (CAR)-based immunotherapy has shown great potential for the treatment of both hematopoietic malignancies and solid tumors. Nevertheless, multiple obstacles still block the development of CAR-based immunotherapy in the clinical setting. In this study, we aimed to summarize the research landscape and highlight the front lines and trends of this field. Methods: Literature published from 2001 to 2021 was searched in the Web of Science Core Collection database. Full records and cited references of all the documents were extracted and screened. Bibliometric analysis and visualization were conducted using CiteSpace, Microsoft Excel 2019, VOSviewer and R software. Results: A total of 5981 articles and reviews were included. The publication and citation results exhibited increasing trends in the last 20 years. Frontiers in Immunology and Blood were the most productive and most co-cited journals, respectively. The United States was the country with the most productive organizations and publications in the comprehensive worldwide cooperation network, followed by China and Germany. June, C.H. published the most papers with the most citations, while Maude, S.L. ranked first among the co-cited authors. The hotspots in CAR-based therapy research were multiple myeloma, safety and toxicity, solid tumors, CAR-engineered immune cells beyond T cells, and gene editing. Conclusion: CAR-based immunotherapy is a promising treatment for cancer patients, and there is an emerging movement toward using advanced gene modification technologies to overcome therapeutic challenges, especially in solid tumors, and to generate safer and more effective universal CAR-engineered cell products.


Subject(s)
Neoplasms , Receptors, Chimeric Antigen , Bibliometrics , Humans , Immunologic Factors , Immunotherapy , Immunotherapy, Adoptive , Neoplasms/therapy , Receptors, Chimeric Antigen/genetics , United States
12.
Front Oncol ; 12: 782058, 2022.
Article in English | MEDLINE | ID: mdl-35345446

ABSTRACT

Objective: To investigate whether TCF7+ T cells constitute an important factor to improve the existing postoperative prediction model for patients with oral squamous cell carcinoma. Method: TCF7+ T cells were detected in the tissues of 167 OSCC patients by multiplex immunofluorescence. The percentage of TCF7+ T cells was transformed into a dichotomous variable, combined with the clinicopathological data for the OSCC patients, and then subjected to univariate and multivariate analyses. The derived independent predictors were then incorporated into risk models to analyze their relationship with the prognosis of patients. Results: The high TCF7+ group had a better prognosis than the low TCF7+ group (OS: p<0.001; RFS: p<0.001). Univariate and multivariate analyses showed that TCF7+ T cells serve as an independent predictor of OSCC (univariate/multivariate analysis: p<0.001). In Cox risk progression models, inclusion of the TCF7+ T cell percentage improved the predictive accuracy of Grade and TNM stage (Grade-OS/RFS: p<0.001; TNM-OS/RFS: p<0.001; TNM+Grade-OS: p<0.001, TNM+Grade-RFS: p=0.004). Inclusion of the TCF7+ T cell percentage improved the clinical utility. Conclusions: TCF7+ T cells can act as an independent predictor for postoperative OSCC patients. The inclusion of TCF7+ T cells improved the predictive accuracy and clinical utility of the nomograms to different degrees.

13.
Cell Prolif ; 55(4): e13207, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35179267

ABSTRACT

OBJECTIVES: This study aimed to clarify the dynamic changes of exhaustion features in T cells during oral carcinogenesis. MATERIALS AND METHODS: Mice were randomly divided into 4NQO group and control group. The exhaustion features of CD4+ and CD8+ T cells of both groups were detected by flow cytometry. Furthermore, multiplex immunohistochemistry was used to evaluate the expression of inhibitory receptors in human normal, dysplastic, and carcinogenesis tissues. Finally, anti-PD-1 antibody treatment was performed at the early premalignant phase of oral carcinogenesis. RESULTS: The proportion of naive T cells in 4NQO group was lower than those in control group, while the proportion of effector memory T cells was higher in 4NQO group. The expression of inhibitory receptors on CD4+ and CD8+ T cells increased gradually during carcinogenesis. In contrast, the secretion of cytokines by CD4+ and CD8+ T cells decreased gradually with the progression stage. Strikingly, those changes occurred before the onset of oral carcinogenesis. The expression of inhibitory receptors on T cells increased gradually as the human tissues progressed from normal, dysplasia to carcinoma. Interestingly, PD-1 blockade at the early premalignant phase could reverse carcinogenesis progression by restoring T cell function. CONCLUSIONS: T-cell dysfunction was established at the early premalignant phase of oral carcinogenesis; PD-1 blockade at the early premalignant phase can effectively reverse T-cell exhaustion features and then prevent carcinogenesis progression.


Subject(s)
CD8-Positive T-Lymphocytes , Programmed Cell Death 1 Receptor , Animals , Carcinogenesis/metabolism , Mice
14.
Int J Oral Sci ; 14(1): 8, 2022 02 14.
Article in English | MEDLINE | ID: mdl-35153298

ABSTRACT

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8+PD1+TCF1+ progenitor exhausted T cells (TCF1+Texprog) and CD8+PD1+TCF1- terminally exhausted T cells (TCF1-Texterm). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1-Texterm represented a greater proportion of CD8+PD1+Tex than TCF1+Texprog in most patients. TCF1+Texprog produced abundant TNFα, while TCF1-Texterm expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1-Texterm exhibited a polyfunctional TNFα+GZMB+IFNγ+ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1-Texterm were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1-Texterm was the major CD8+PD1+Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1-Texterm was associated with greater Treg abundance.


Subject(s)
CD8-Positive T-Lymphocytes , Head and Neck Neoplasms , Head and Neck Neoplasms/therapy , Humans , Immunotherapy/methods , Prognosis , Programmed Cell Death 1 Receptor , Squamous Cell Carcinoma of Head and Neck/therapy , Tumor Microenvironment , Tumor Necrosis Factor-alpha
15.
Oral Oncol ; 119: 105348, 2021 08.
Article in English | MEDLINE | ID: mdl-34044317

ABSTRACT

OBJECTIVES: Despite substantial advances in treatment, clinical outcomes for oral squamous cell carcinoma (OSCC) remain unsatisfactory. Tumor-infiltrating lymphocytes (TILs) are an important prognostic factor for patients and are heterogeneous. Some studies have suggested that TCF1/TCF7+ T cells and tertiary lymphatic structure/organ (TLS) play an important role in tumor immunity. However, how they affect tumor immunity and whether they are related to prognosis in OSCC have not been reported in detail. MATERIALS AND METHODS: We isolated OSCC cells and performed single-cell RNA sequencing (scRNA-seq). We used immunohistochemistry (IHC) to analyze the relationship between TLSs and prognosis. Multiplex immunohistochemistry (MIHC), flow cytometry (FCM) and spatial analysis were performed to verify the characteristics of TCF1/TCF7+ T cells. The prognostic significance and upstream regulatory network of the TCF1/TCF7+ T cell subpopulation were determined by multivariate analysis and Scenic software. RESULTS: We found a strong association between TCF1/TCF7+ T cell subsets, TLSs and prognosis. The results suggested that TCF1/TCF7+ T cells express high levels of TLS-related genes and low levels of immune checkpoint molecules. Finally, we found that TCF1/TCF7+ T cells were significantly associated with favorable outcomes. We also describe the upstream drivers that these cells rely on. CONCLUSIONS: TCF1/TCF7+ T cells could be used as a new therapeutic target to regulate the immune response of OSCC and are expected to be a new prognostic marker.


Subject(s)
Mouth Neoplasms , Squamous Cell Carcinoma of Head and Neck , T-Lymphocyte Subsets , Tertiary Lymphoid Structures , Hepatocyte Nuclear Factor 1-alpha , Humans , Lymphocytes, Tumor-Infiltrating , Mouth Neoplasms/diagnosis , Mouth Neoplasms/immunology , Prognosis , Squamous Cell Carcinoma of Head and Neck/diagnosis , Squamous Cell Carcinoma of Head and Neck/immunology , T Cell Transcription Factor 1
16.
Clin Cancer Res ; 27(13): 3757-3771, 2021 07 01.
Article in English | MEDLINE | ID: mdl-33811153

ABSTRACT

PURPOSE: The limited efficacy of chimeric antigen receptor (CAR) T-cell therapies with solid malignancies prompted us to test whether epigenetic therapy could enhance the antitumor activity of B7-H3.CAR T cells with several solid cancer types. EXPERIMENTAL DESIGN: We evaluated B7-H3 expression in many human solid cancer and normal tissue samples. The efficacy of the combinatorial therapy with B7-H3.CAR T cells and the deacetylase inhibitor SAHA with several solid cancer types and the potential underlying mechanisms were characterized with in vitro and ex vivo experiments. RESULTS: B7-H3 is expressed in most of the human solid tumor samples tested, but exhibits a restricted expression in normal tissues. B7-H3.CAR T cells selectively killed B7-H3 expressing human cancer cell lines in vitro. A low dose of SAHA upregulated B7-H3 expression in several types of solid cancer cells at the transcriptional level and B7-H3.CAR expression on human transgenic T-cell membrane. In contrast, the expression of immunosuppressive molecules, such as CTLA-4 and TET2, by T cells was downregulated upon SAHA treatment. A low dose of SAHA significantly enhanced the antitumor activity of B7-H3.CAR T cells with solid cancers in vitro and ex vivo, including orthotopic patient-derived xenograft and metastatic models treated with autologous CAR T-cell infusions. CONCLUSIONS: Our results show that our novel strategy which combines SAHA and B7-H3.CAR T cells enhances their therapeutic efficacy with solid cancers and justify its translation to a clinical setting.


Subject(s)
B7 Antigens , Histone Deacetylase Inhibitors/therapeutic use , Immunotherapy, Adoptive , Neoplasms/therapy , Receptors, Chimeric Antigen/therapeutic use , Animals , Combined Modality Therapy , Humans , Mice , Tumor Cells, Cultured
17.
Oral Dis ; 27(7): 1667-1677, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33125794

ABSTRACT

OBJECTIVE: This study was aimed to analyze the role of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) expression on T cells in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TILs) were collected from OSCC patients. The correlation between TIGIT expression and clinicopathologic features was analyzed by chi-square test. Phenotypic and functional study of TIGIT+ T cells were performed by flow cytometry. RESULTS: TIGIT was highly expressed on T cells from PBMC and TILs. High expression of TIGIT on CD4+ T cells (19.0%) and CD8+ T cells (35.9%) was also associated with higher T stage and nodal invasion. Moreover, TIGIT+ CD4+ and TIGIT+ CD8+ T cells sorted from OSCC patients showed a dysfunctional phenotype (low cell proliferation and low secretion of IL-2, TNF-α and IFN-γ), and TIGIT+ CD4+ T cells exhibited inhibitory function (high expression of Foxp3 and high amounts of IL-10). Importantly, TIGIT blockade can enhance the proliferation ability and effective cytokine production (IL-2, TNF-α, and IFN-γ) of CD4+ and CD8+ T cells from OSCC patients in vitro. CONCLUSIONS: TIGIT-expressing T cells exhibit a lower effector cytokine-releasing phenotype in OSCC patients.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , CD8-Positive T-Lymphocytes , Humans , Leukocytes, Mononuclear , Receptors, Immunologic , Squamous Cell Carcinoma of Head and Neck
18.
Int J Oral Sci ; 12(1): 24, 2020 09 15.
Article in English | MEDLINE | ID: mdl-32934197

ABSTRACT

Tertiary lymphoid structures (TLS) are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis. However, the prognostic value of TLSs in oral squamous cell carcinoma (OSCC) is largely unknown, and the association between tumour infiltrating lymphocytes (TILs) and TLSs has been rarely explored in OSCC. In this study, associated markers of TLS, including peripheral node address (PNAd) in high endothelial venules, CD20 in B cells and CD3 in T cells, were examined in 168 OSCC patients, and survival analysis was performed between TLS-positive and TLS-negative cohorts. We detected the presence of TILs by staining CD8+ cytotoxic T cells and CD57+ NK cells as well. TLSs appeared as highly organized structures in 45 (26.8%) cases. TLS-positive patients had a better 5-year overall survival (OS) rate (88.9% vs. 56.1%, P < 0.001) and relapse-free survival (RFS) rate (88.9% vs. 63.4%, P = 0.002). Moreover, the presence of TLS was an independent prognostic factor for both the 5-year OS rate (hazard ratio [HR] = 3.784; 95% confidence interval [CI], 1.498-9.562) and RFS rate (HR = 3.296; 95% CI, 1.279-8.490) in multivariate analysis. Furthermore, a higher density of CD8+ T cells and CD57+ NK cells was found in TLS-positive sections than in TLS-negative counterparts (P < 0.001), and their combination provided a higher predictive accuracy (AUC = 0.730; 95% CI, 0.654-0.805). In conclusion, our results suggest that TLS is an independent positive prognostic factor for OSCC patients. These findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Tertiary Lymphoid Structures , Humans , Lymphocytes, Tumor-Infiltrating , Neoplasm Recurrence, Local , Prognosis , Squamous Cell Carcinoma of Head and Neck
19.
Oral Oncol ; 110: 104943, 2020 11.
Article in English | MEDLINE | ID: mdl-32919362

ABSTRACT

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.


Subject(s)
Lymphocytes, Tumor-Infiltrating/immunology , Mutation , Squamous Cell Carcinoma of Head and Neck/etiology , Squamous Cell Carcinoma of Head and Neck/mortality , Adult , Aged , Algorithms , Biomarkers, Tumor , Computational Biology/methods , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Squamous Cell Carcinoma of Head and Neck/pathology , Transcriptome , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology
20.
Sci Rep ; 10(1): 2662, 2020 02 14.
Article in English | MEDLINE | ID: mdl-32060343

ABSTRACT

In the last few years, V-domain Ig-containing suppressor of T cell activation(VISTA) has been reported as a prognostic biomarker in articles including various solid tumours. However, their conclusions have been controversial. For this reason, we performed this meta-analysis to further verify the prognostic value of VISTA in solid tumours. All relevant literature was identified from PubMed, Embase, the Cochrane Library and Web of Science. Ten studies, including 2, 440 patients, were eligible for the analysis. The pooled results showed that high expression of VISTA was associated with favourable overall survival (OS) than that seen with low expression of VISTA (7 studies, hazard ratio (HR) = 0.75, 95% confidence interval (CI): 0.66-0.86, P < 0.001). In addition, high expression of VISTA significantly correlated with high numbers of CD8 (+) tumour infiltrating lymphocytes (TILs) (3 studies, risk ratio (RR) = 1.80, 95% CI: 1.41-2.31, P < 0.001). In conclusion, these results indicate that VISTA is a potential prognostic biomarker in solid tumours.


Subject(s)
B7 Antigens/metabolism , Neoplasms/diagnosis , Neoplasms/metabolism , CD8-Positive T-Lymphocytes/immunology , Disease-Free Survival , Female , Humans , Lymphocyte Count , Lymphocytes, Tumor-Infiltrating/immunology , Male , Neoplasms/immunology , Prognosis , Publication Bias
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