Distinct expression of perforin and granzyme B in lip and oral cavity squamous cell carcinoma

J Oral Pathol Med (2011) 40 : 380–384 Background: Perforin and granzyme B (GB) are the main constituents of cytotoxic T‐lymphocyte granules, and they have important roles in preventing the initiation and progression of cancer. Methods: The aim of this study was to compare the expression of CD8⁺/perforin⁺ double‐staining and GB⁺ cells, by immunohistochemistry, in primary oral cavity squamous cell carcinoma (OCSCC), lip squamous cell carcinoma (LSCC), non‐dysplastic leukoplakia (LK), dysplastic LK, actinic cheilitis (AC), oral lichen planus (LP) and normal oral mucosa. Results: Our results showed a higher expression of CD8⁺/perforin⁺ and GB⁺ cells in LSCC when compared with the samples of OCSCC, non‐dysplastic and dysplastic LK, AC, oral LP and normal oral mucosa. In addition, increased CD8⁺/perforin⁺ and GB⁺ cell numbers were observed in all pre‐malignant lesions (non‐dysplastic LK, dysplastic LK, AC) when compared with the control. Conclusions: Perforin and GB proteins may contribute to antitumoural immunity, leading to the direct killing of tumour cells; however, it seems to occur more effectively in LSCC than OCSCC.     

Midkine expression in oral squamous cell carcinoma and leukoplakia

J Oral Pathol Med (2012) 41 : 21–26 Background: Midkine (MK), a 13‐kDa heparin‐binding growth factor, is overexpressed in various human cancers. However, its role in the development and progression of oral cavity squamous cell carcinoma (OCSCC) is still unclear. Thus, the aim of this study was to evaluate the expression of MK in samples of OCSCC, leukoplakia, and healthy oral mucosa (control). Methods: Surgically excised specimens from patients with primary OCSCC (n = 28) were immunostained for MK, Ki‐67, PCNA, p53, bcl‐2, Bax, and CD31. Besides this, MK expression was also investigated in leukoplakia and normal oral mucosa. The relationship of MK⁺ cells with clinical parameters (tumor location, tumor size, lymph node metastasis, and survival) and microscopic parameters (WHO histological grading, intensity of inflammation, proliferation index, apoptosis, and angiogenesis) was also evaluated. Results: The results showed that MK expression was increased in OCSCC in relation to leukoplakia and normal mucosa. Furthermore, MK expression was increased in late‐stage tumors (T3/T4) compared with early‐stage lesions (T1/T2). MK‐positive lesions also showed increased expression of the anti‐apoptotic protein bcl‐2. Conclusion: OCSCC, particularly late‐stage tumors, exhibits increased MK expression, which may be involved in tumor progression via upregulation of anti‐apoptotic genes, as shown by the augmented bcl‐2 positivity in MK‐positive tumors.     

The prognostic role of tumour‐infiltrating lymphocytes in oral squamous cell carcinoma: A meta‐analysis

It has been suggested that tumour‐infiltrating lymphocytes (TILs) are associated with the progression of oral squamous cell carcinoma (OSCC). However, the prognostic value of TILs is inconclusive due to the heterogeneity of immune cells within the tumour microenvironment. In this meta‐analysis, we aimed to assess the prognostic value of TILs in OSCC. The PubMed, Cochrane, Embase, Scopus and Web of Science databases were searched up to April 20, 2019, and 33 studies were ultimately included in this meta‐analysis. Our pooled meta‐analysis showed that high infiltration of CD8⁺ TILs, CD45RO⁺ TILs and CD57⁺ TILs favoured better overall survival (OS). However, high infiltration of CD68⁺ macrophages and CD163⁺ macrophages was associated with poor prognosis in OSCC. These findings suggest that CD8⁺ TILs, CD45RO⁺ TILs, CD57⁺ TILs, CD68⁺ macrophages and CD163⁺ macrophages might serve as novel prognostic factors and therapeutic targets in OSCC.     

Expression of CD163, interleukin‐10, and interferon‐gamma in oral squamous cell carcinoma: mutual relationships and prognostic implications

Tumor‐associated macrophages (TAMs) and their associated inflammatory cytokines represent the major inflammatory component of the stroma of many tumors and can affect prognosis in the case of neoplasms. The objective of this study was to determine the prognostic significance of CD163⁺ cells, interleukin‐10 (IL‐10), and interferon‐gamma (IFN‐γ) in oral lesions associated with oral squamous cell carcinoma (OSCC). The levels of CD163, IFN‐γ, and IL‐10 in the tissue samples of 240 patients with OSCC and 58 patients with other oral lesions were assessed by immunohistochemistry. Individuals with low IFN‐γ levels, high IL‐10 levels, and low CD163 levels were of special concern with respect to OSCC progression. We found that high levels of CD163, or a combination of low IFN‐γ levels, high IL‐10 levels, and low CD163 levels, were associated with poorer overall survival (OS). CD163⁺ cells provide better predictive power for OS in comparison with traditional markers, such as clinical stage and lymph node metastasis. Therefore, CD163⁺ cells may be effective prognostic predictors of OSCC. IL‐10 may also indicate poor outcomes when IFN‐γ secretion is low and the cells are CD163^?.     

Evaluation of Cd8+ and natural killer cells defense in oral and oropharyngeal squamous cell carcinoma

Purpose

The aim of this study was to evaluate the population of CD8+ and natural killer (NK) cells in samples of oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinoma.

Role of human papillomavirus infection in carcinogenesis of oral squamous cell carcinoma with evidences of prognostic association

J Oral Pathol Med (2012) 41 : 9–15 Background: Betel nut chewing, cigarette smoking and alcohol drinking are thought to be major environmental risk factors responsible for the development of oral squamous cell carcinomas. Oncogenic human papillomavirus infections have a well‐established association with uterine cervical carcinoma. However, little is known about the exact role of human papillomavirus infections in oral squamous cell carcinomas. This study is designed to elucidate the role of human papillomavirus infections in cancer development and prognosis of oral squamous cell carcinomas. Methods: Molecular techniques including in situ hybridization and immunohistochemistry of p16^INK4A and p53 for evidences of human papillomavirus in tissue micro‐arrays were investigated. Results: Twenty‐four of 65 cases of oral squamous cell carcinomas were found positive for in situ hybridization and 14 were found positive for p16^INK4A. The majority of cases without the evidence of human papillomavirus were related to p53 over‐expression. There were statistically significant correlations between the results of human papillomavirus test and size or extent of the tumor (P = 0.003) or the stage of oral squamous cell carcinomas (P = 0.015). Kaplan–Meier plot analysis demonstrated a tendency of longer survival in cases of oral squamous cell carcinomas with the evidence of human papillomavirus or positive p16 ^INK4A. Conclusions: Human papillomavirus infections may play a unique role in oral carcinogenesis. Our data strongly suggest that human papillomavirus‐positive oral squamous cell carcinomas comprise a distinct clinical and pathological disease entity that appears related to a better outcome with longer survival and bears a causally associated relationship different from other carcinogenic mechanisms.     

Role of angiogenic and non-angiogenic mechanisms in oral squamous cell carcinoma: correlation with histologic differentiation and tumor progression

BACKGROUND: Angiogenesis has been demonstrated to associate with various measures of tumor aggressiveness in many human malignancies. However, studies of tumor angiogenesis in oral squamous cell carcinoma (SCC) are still unclear. Recent studies indicate non-angiogenesis mechanism (tumor-lined vessel) may exist in certain tumors. Therefore, we investigate microvessel density (MVD) and tumor-lined vessel in oral SCC. METHODS: Peritumoral and intratumoral MVD were measured by immunohistochemical staining. Tumor-lined vessels were identified by double staining. Statistical analysis of peritumoral and intratumoral MVD and presence of tumor-lined vessels with clinicopathologic parameters was performed. RESULTS: The results showed peritumoral MVD increased with disease progression and further increases of intratumoral MVD was detected by CD31 and CD34. Non-angiogenesis, tumor-lined vessel, presented in oral SCC and correlated significantly with tumor size, stage, and histologic differentiation. CONCLUSION: Our results suggest at the initiation of oral SCC, increasing vascularity is observed at the periphery of the tumor. As the tumor continues to grow, further increases of intratumoral vascularity and the presence of tumor-lined vessels are associated with cancer progression.     

Immunohistochemical co-localization of lymphatics and blood vessels in oral squamous cell carcinomas

BACKGROUND: Differentiating lymphatic vessels from blood vessels is difficult, partly due to the lack of a specific method for identifying lymphatics. A new lymphatic vessel-reactive antibody, D2-40 has recently become commercially available. We examined the selectivity of D2-40 for lymphatics in oral neoplastic lesions for discrimination from blood vessels. METHODS: Formalin-fixed, paraffin-embedded sections of oral lymphangiomas (n = 3), oral hemangiomas (n = 7), and oral squamous cell carcinomas (OSCC, n = 46) were double immunostained with D2-40 and anti-CD34 monoclonal antibodies (MoAb) using ENVISION-polymer technique with 5-bromo-4-chloro-3-indoxyl-phosphate (BCIP)/nitroblue tetrazolium chloride (NBT) and 3,3'-diaminobenzidine (DAB) as color reagents, respectively. Results: In the oral lymphangiomas and hemangiomas D2-40 was detected in all lymphatics, while all blood vessels were positive for CD34. In OSCC, number of vessels for lymphatics (P < 0.01) and for blood vessels in the perineoplastic areas were significantly greater than those in intratumoral areas. CONCLUSIONS: These results indicate that lymphatic proliferation might be much more extensive in the peritumoral area than intratumoral.     

The presence of Merkel cells and CD10‐ and CD34‐positive stromal cells compared in benign and malignant oral tumors

Background: To describe sequential changes in Merkel cells (MC), and CD10⁺ and CD34⁺ stromal cells (SC) during the transition from benign to malignant oral lesions and correlate with clinicopathologic parameters. Materials and methods: Changes in cytokeratin 20‐positive (CK20⁺) Merkel cells, CD10⁺ and CD34⁺ SC were immunohistochemically examined in specimens of 28 oral verrucous carcinomas (VC), 32 squamous cell carcinomas (SCC) and 36 benign squamous lesions (BSL). Immunoreactivity and localized inflammation were measured quantitatively and/or semiquantitatively, and between‐group results were statistically compared. Results: The mean number of CD34⁺ SC was significantly lower in VC (57.36) and SCC (33.81) than BSL (351.56, P < 0.001). However, the three tumor types had similar staining level and number of CD10⁺ SC. We found a significant difference in the density of MC between BSL and VC (P < 0.001) or SCC (P < 0.001). The number of CK20⁺ MC was significantly lower in highly inflamed specimens than mildly inflamed specimens (P = 0.001). Conclusion: CD34⁺ SC and to a lesser extent MC, but not CD10⁺ SC, reveal statistically different density during the transition from benign to malignant oral lesions. The correlations between the CD34⁺ SC expression and squamous lesions may be associated with epithelial dysplasia and/or tumor invasion.     

Prognostic significance of extranodal extension in oral cavity squamous cell carcinoma with occult neck metastases

A grade of extranodal extension (ENE) may advance risk stratification related to survival in patients with metastatic oral cavity squamous cell carcinoma (OCSCC). Pathological examination of 174 OCSCC patients who were primarily surgically treated with tumour resection and elective neck dissection was performed. Data of ENE presence, its extent (in millimetres), patients and tumour characteristics were statistically analysed with respect to disease-free survival (DFS) and overall survival (OS). Ninety patients (51.7%) were identified with occult nodal disease, with 41 patients (23.6%) presenting with ENE. Receiver operating characteristics (ROC) curve analysis set the threshold at 1.9 mm as an optimal ENE cut-off regarding both DFS and OS. Patients were divided by extent into minor ENE (≤1.9 mm) and major ENE (>1.9 mm) subgroups. The subgroup with minor ENE had significantly higher DFS and OS rates compared with major ENE. ENE cut-off threshold at 1.9 mm discriminates low and high-risk subgroups of patients with occult OCSCC in terms of DFS and OS.     

Evaluation of survivin as a prognostic marker in oral squamous cell carcinoma

J Oral Pathol Med (2010) 39 : 368–375 Background: Poor prognosis of oral squamous cell carcinoma (OSCC) is partly attributed to the lack of significant tumor marker for accurate staging and prognostication. We have evaluated survivin, which is a member of the inhibitor of apoptosis family as a cancer marker associated with proliferation, angiogenesis, oral carcinogenesis, and OSCC patient survival, as we reported a prognostic significance of survivin expression in lymph node previously. Methods: To evaluate survivin expression in six OSCC cell lines, Western blotting was performed. Hamster oral carcinogenesis model was used to observe changes of survivin expression in oral carcinogenesis. Finally, we assessed the diagnostic and prognostic significance of survivin in a series of 38 primary OSCC through immunohistochemistry (CD31, PCNA) and Kaplan–Meier’s test. Results: Survivin expression was detected in all OSCC cell lines at a varying level but not observed in normal gingival keratinocyte cells. In hamster model, survivin expression was observed from 8 weeks through 16 weeks and the intensity of expression became strong until 16 weeks. Clinicopathological analysis revealed a significant correlation between survivin expression and lymph node metastasis (P = 0.006) and proliferation (P < 0.001). However, there was no significant relationship with differentiation, micro vessel density, and cancer stage based on TNM. Survivin overexpression had a significant negative effect on survival of patients. Conclusions: These results demonstrate the significant relationship between survivin expression and oral carcinogenesis and aggressiveness of OSCC including survival rate of patient. Survivin therefore may be used as a significant cancer marker to gain prognostic information of OSCC.     

Expression of CD44 (NKI-P1) in oral squamous cell carcinoma associated vascular endothelial cells: A relationship to tumor angiogenesis

BackgroundOral squamous cell carcinoma is characterized by high degree of local invasion with metastasis as well as characteristic angiogenic features. Angiogenesis is a critical step in the growth and metastasis of tumors. Cluster of differentiation 44 (CD44) is a cell surface glycoprotein which is widely expressed in both physiological and pathological conditions.AimThe study was designed to assess the expression of CD44 (NKI-P1) in oral squamous cell carcinoma associated endothelial cells and to correlate this expression with matrix metalloprpteinase-9 (MMP-9) and transforming growth factor-beta (TGF- β) expression immunohistochemically.Materials and methodsOne hundred fourteen archival oral squamous cell carcinoma cases were used in this study. Immunohistochemistry was performed for CD44 (NKI-P1), Ki-67, cluster of differentiation 31(CD31), podoplanin (D2-40), MMP-9 and TGF- β. Microvessel density was also determined morphologically. Results: CD44 was expressed in (CD31+/ Podoplanin –) blood vascular endothelial cells in a strong cytoplasmic fashion. In addition, the extracellular matrix proteins (MMP-9 and TGF-β were expressed in oral squamous cell carcinoma stroma which was enriched with CD44 + blood vessels. The mean numbers of microvessel density in connective tissue beneath normal epithelium and different grades of oral squamous cell carcinoma stroma were 5.8, 22.1, 22.4 and 23.5, respectively with the P-value < 0.05, where a significant statistical difference between microvessel density in the connective tissue beneath normal epithelia and stroma of all grades of oral squamous cell carcinoma was found. Conclusion: CD44 (NKI-P1) is considered a potential marker of oral squamous cell carcinoma angiogenesis and it can be used as a valuable biomarker of tumor invasion and as a therapeutic target for anti-angiogenic therapies.     

Intratumoral lymphangiogenesis in oral squamous cell carcinoma and its clinicopathological significance

Lymphatic metastasis has always been regarded as a major prognostic indicator for disease progression and as a guide for therapeutic strategies to oral squamous cell carcinoma (OSCC), but to date, how tumor cells access and spread via the lymphatics have not been fully elucidated. Whether tumor cells metastasize by expansion and invasion of pre‐existing peritumoral lymphatics or by the induction and invasion of newly formed lymphatics within tumors is controversial. In order to address this issue and find out the clinicopathological significance of intratumoral lymphangiogenesis, we investigated 86 archival specimens from patients with OSCC, quantitating lymph vessels by immunostaining with D2‐40. We also quantified lymphatic invasion and examined the possible associations of all the above parameters with clinicopathological features and outcome. Higher intratumoral lymphatic density (ILD) and peritumoral lymphatic density (PLD) were both significantly associated with the presence of lymph node metastasis at the time of diagnosis and the outcome of the post‐operation biopsy of 77 patients (P = 0.001). Higher ILD was significantly associated with a higher incidence of intratumoral lymphatic invasion, peritumoral lymphatic invasion and recurrence of tumor (P = 0.001 and P = 0.041 and P = 0.001, respectively). Patients with higher ILD exhibited shorter 5‐year cumulative and disease‐free survival (P = 0.001). Thus, lymphangiogenesis indeed occurs in oral squamous cell carcinoma; ILD might be used as an index to inflect the aggression of the disease, to evaluate the status of lymphatic metastasis, to separate patients at higher risk of an adverse clinical outcome.     

局部注射IL-2联合化疗对口腔鳞癌浸润淋巴细胞的影响

目的　评价IL-2局部注射联合化疗对口腔鳞癌局部免疫反应的影响。方法　34例T3、T4期口腔鳞癌患者随机分成2组接受术前治疗,其中23例行免疫化疗(IL-2局部注射合并PVP化疗),11例行单纯化疗。比较 2组患者治疗前后肿瘤浸润T淋巴细胞亚群和B淋巴细胞的变化。结果　免疫化疗组治疗前后CD4+,CD8+, CD20+相对值分别为36·96,35·65,28·65和56·61,38·52,38·70。治疗后CD4+,CD20+细胞数较治疗前明显增加 (P<0·01)。单纯化疗组治疗前后CD4+,CD8+,CD20+细胞数均无显著差异(P>0·05)。结论　IL-2局部注射联合化疗对增强口腔鳞癌患者局部免疫功能具有重要意义。     

The role of SPP1 as a prognostic biomarker and therapeutic target in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies and has a low 5-year survival rate. Mounting evidence suggests that oral potentially malignant disorders, such as oral leukoplakia (OLK), may progress to HNSCC. Given that OLK and HNSCC are often insidious and asymptomatic, the identification of markers of OLK malignant transformation and therapeutic targets in HNSCC is critical. Using various online tools and publicly available gene expression datasets, the secreted phosphoprotein 1 gene (SPP1) was identified as a significant differentially expressed gene among OLK, HNSCC, and non-cancerous tissues. SPP1 mRNA levels were elevated in HNSCC tissues and were associated with cancer stage, tumor grade, and human papillomavirus infection status. High SPP1 mRNA levels were correlated with poor overall survival of HNSCC patients. In contrast, SPP1 mutations were not significantly associated with overall survival, although their frequency in HNSCC was very low (0.6%). Furthermore, SPP1 expression levels in HNSCC were positively correlated with the infiltration of CD4⁺ cells, macrophages, neutrophils, and dendritic cells. The study results suggest that SPP1 may represent a diagnostic and prognostic biomarker, as well as a potential therapeutic target in HNSCC.     

Expression of p53 in oral mucosal hyperplasia, dysplasia and squamous cell carcinoma

OBJECTIVE: To assess p53 expression in a range of oral mucosal lesions and to relate the results to the clinical outcome in patients with dysplastic oral mucosal lesions and oral squamous cell carcinomas (OSCC).
MATERIALS AND METHODS: Archival tissue was available for eight cases of normal oral mucosa, 50 cases of oral mucosal hyperplasia, 41 cases of oral mucosal dysplasia and 48 cases of OSCC. The monoclonal antibody DO-7, reactive to p53 protein, was applied to paraffin-embedded sections using microwave pretreatment and immu-nohistochemical techniques.
RESULTS: The results showed that normal oral mucosa did not express p53.Positive nuclear staining was found in 18/50 (36%) cases of hyperplasia, 35/41 (85%) cases of dysplasia and 45/48 (94%) cases of OSCC.None of the p53 negative dysplasias progressed, while 19% of p53 positive cases of dysplasia recurred following excision and 11% of the cases underwent neoplastic transformation. Five out of 10 (50%) cases of severe dysplasia which were p53 positive resolved.
CONCLUSION: The proportion of cases with positive p53 expression increased from hyperplasia to dysplasia to OSCC. These results may indicate an involvement of p53 in neoplastic transformation as well as in proliferative events although the presence or absence of p53 staining could not be used to predict the outcome of potentially malignant oral mucosal lesions.     

What has the National Cancer Database taught us about oral cavity squamous cell carcinoma?

The wealth of data in the National Cancer Database (NCDB) has allowed numerous studies investigating patient, disease, and treatment-related factors in oral cavity squamous cell carcinoma (OCSCC); however, to date, no summation of these studies has been performed. The aim of this study was to provide a concise review of the NCDB studies on OCSCC, with the hopes of providing a framework for future, novel studies aimed at enhancing our understanding of clinical parameters related to OCSCC. Two databases were searched, and 27 studies published between 2002 and 2020 were included. The average sample size was 13,776 patients (range 356–50,896 patients). Four areas of research focus were identified: demographic and socioeconomic status, diagnosis, prognosis, and treatment. This review highlights the impact of age, sex, ethnicity, and socioeconomic status on the prognosis and management of OCSCC, describes the prognostic factors, and details the modalities and indications for neck dissection and adjuvant therapy in OCSCC. In conclusion, the NCDB is a very valuable resource for clinicians and researchers involved in the management of OCSCC, offering an incomparable perspective on a large dataset of patients. Future developments regarding hospital information management, review of data accuracy and completeness, and wider accessibility will help clinicians to improve the care of patients affected by OCSCC.     

Apigenin inhibited hypoxia induced stem cell marker expression in a head and neck squamous cell carcinoma cell line

ObjectiveCancer stem cells contribute to tumor recurrence, and a hypoxic environment is critical for maintaining cancer stem cells. Apigenin is a natural product with anticancer activity. However, the effect of apigenin on cancer stem cells remains unclear. Our aim was to investigate the effect of apigenin on cancer stem cell marker expression in head and neck squamous cell carcinoma cells under hypoxia.DesignWe used three head and neck squamous cell carcinoma cell lines; HN-8, HN-30, and HSC-3. The mRNA expression of cancer stem cell markers was determined by semiquantitative RT-PCR and Real-time PCR. The cytotoxic effect of apigenin was determined by MTT colorimetric assay. Flow cytometry was used to reveal the number of cells expressing cancer stem cell surface markers.ResultsHN-30 cells, a cancer cell line from the pharynx, showed the greatest response to hypoxia by increasing their expression of CD44, CD105, NANOG, OCT-4, REX-1, and VEGF. Apigenin significantly decreased HN-30 cell viability in dose- and time-dependent manners. In addition, 40 μM apigenin significantly down-regulated the mRNA expression of CD44, NANOG, and CD105. Consistent with these results, the hypoxia-induced increase in CD44⁺ cells, CD105⁺ cells, and STRO-1⁺ cells was significantly abolished by apigenin.ConclusionApigenin suppresses cancer stem cell marker expression and the number of cells expressing cell surface markers under hypoxia.     

Nuclear fractal dimension in oral squamous cell carcinoma: a novel method for the evaluation of grading,staging, and survival

Fractal dimension (FD) in tissue specimens from patients with oral squamous cell carcinoma (OSCC) was evaluated. FD values in different stages of OSCC, and the correlations with clinicopathological variables and patient survival were investigated. Histological sections from OSCC and control non‐neoplastic mucosa specimens were stained with hematoxylin–eosin for pathological analysis and with Feulgen for nuclear evaluation. FD in OSCC groups vs. controls revealed statistically significant differences (P < 0.001). In addition, a progressive increase of FD from stage I and II lesions and stage III and IV lesions was observed, with statistically significant differences (P = 0.003). Moreover, different degrees of tumor differentiation showed a significant difference in the average nuclear FD values (P = 0.001). A relationship between FD and patients' survival was also detected with lower FD values associated to longer survival time and higher FD values with shorter survival time (P = 0.034). These data showed that FD significantly increased during OSCC progression. Thus, FD could represent a novel prognostic tool for OSCC, as FD values significantly correlated with patient survival. Fractal geometry could give insights into tumor morphology and could become an useful tool for analyzing irregular tumor growth patterns.     

Tim-3在口腔鳞癌患者外周血NK细胞的表达及意义

目的:探讨T细胞免疫球蛋白粘蛋白分子-3(Tim-3)在口腔鳞癌患者外周血自然杀伤细胞(NK细胞)上的表达及其临床意义.方法:应用流式细胞仪检测72例口腔鳞癌患者和40例健康对照者外周血CD3-CD56+ NK细胞表面Tim-3表达水平,分析其与口腔鳞癌患者临床病理特征的关系.结果:口腔鳞癌患者外周血NK细胞的百分率为(9.30±2.52)％,显著低于健康对照组(17.36±3.15)％ (P＜0.001).口腔鳞癌患者外周血NK细胞表达Tim-3的百分率为(14.35±6.35)％,显著高于健康对照组(1.78±0.86)％(P＜0.001),且与肿瘤临床分期、分化程度及淋巴结转移显著相关(P＜0.01).结论:口腔鳞癌患者外周血NK细胞表达降低,Tim-3在口腔鳞癌NK细胞的表达上调可能与口腔鳞癌的发生发展有关.