Malignant transformation of oral lichen planus: a retrospective study of 565 Japanese patients.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory oral mucosa disease that is recognized as an oral potentially malignant disorder. However, the potentially malignant nature of OLP remains unclear. METHODS: We designed this study to examine the demographic and clinical characteristics of patients with OLP and evaluate the associated malignant transformation rate. A total of 565 patients with a clinical and histopathological diagnosis of OLP who presented at our department between 2001 and 2017 were retrospectively studied. Patients who had clinical and histopathological features of oral lichenoid lesions (OLLs) classified as oral lichenoid contact lesions, oral lichenoid drug reactions and oral lichenoid lesions of graft-versus-host disease were excluded. RESULTS: The study population included 123 men and 442 women aged 21-93 years (mean ± standard deviation, 60.5 ± 11.8). The 565 patients were followed up for a duration of 55.9 ± 45.3 months, during which 4 (0.7%) patients developed squamous cell carcinoma (SCC). In three of these 4 patients who developed SCC, the clinical type of OLP was the red type. CONCLUSIONS: Our results suggested that OLP was associated with a low risk of malignant transformation. We recommend regular follow-up for OLP patients and clear differentiation of oral epithelial dysplasia and OLLs to enable early detection of malignant transformation. Further investigation of the clinical risk factors associated with malignant transformation is necessary.

Quantitation and distribution of metallic elements in sequestra of medication-related osteonecrosis of jaw (MRONJ) using inductively coupled plasma atomic emission spectroscopy and synchrotron radiation X-ray fluorescence analysis.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive agents like bisphosphonates. Abnormal concentrations of various trace metallic elements contained in bone minerals have been associated with MRONJ. In this study, we focused on trace metallic elements contained in the MRONJ sequestrum; their content and distribution were compared to those in osteomyelitis and non-inflammatory bones using inductively coupled plasma atomic emission spectroscopy (ICP-AES) and synchrotron radiation X-ray fluorescence analysis (SR-XRF). On ICP-AES analyses, various trace elements (Co, Cr, Cu, Fe, K, Mg, Ni, Sb, Ti, V, Pb) were significantly more in MRONJ sequestra than non-inflammatory bones. The Cu content was significantly higher in MRONJ sequestra than osteomyelitis and non-inflammatory bones. The Cu content in MRONJ sequestra was high even after decalcification. Additionally, Cu was distributed along the trabecular structures in decalcified MRONJ specimens, as observed using SR-XRF analysis. Therefore, this study was indicative of the characteristic behavior of Cu in MRONJ.

Clinical Course of Oral Squamous Cell Carcinoma in Patients on Immunosuppressant and Glucocorticoid Therapy.

PURPOSE: Depressed immune function is a serious adverse effect of long-term immunosuppressant or steroid administration at doses that exceed the physiologically required amount. The purpose of this study was to determine the effects of immunosuppression on carcinogenesis, particularly malignant tumor development, in patients with oral squamous cell carcinoma who had immunosuppression because of immunosuppressant therapy with or without steroid therapy administered for different underlying diseases. MATERIALS AND METHODS: In this retrospective chart review, 886 patients with oral squamous cell carcinoma who received treatment at the authors' department from April 2001 through December 2011 were included. Their clinical characteristics; tumor, node, and metastasis (TNM) stage; initial treatment for the primary cancer; mode of cervical lymph node metastasis; incidence rate of distant metastases; white blood cell, neutrophil, and lymphocyte counts on initial examination; and therapeutic outcomes were evaluated and compared between patients on and those not on immunosuppressant therapy with or without steroid therapy. Survival rates were calculated using the Kaplan-Meier method. RESULTS: Fourteen eligible patients (5 men, 9 women; mean age, 65.2 yr) were identified who were on immunosuppressant therapy with or without steroid therapy. They exhibited considerably more metastases, extracapsular spread, and distant metastases, and the number of metastases and extracapsular spread were statistically significant (P = .0213, P = .042, respectively). In 9 patients, total lymphocyte count in the peripheral blood was no higher than 1,500/µL, indicating the lower limit of the normal range. One patient died of recurrence of the primary tumor. Another patient died of cervical lymph node recurrence. Distant metastases occurred in 2 patients. The cumulative disease-specific 5-year survival rate of patients receiving immunosuppressive therapy was 62.3% and that of patients with cervical lymph node metastasis was 25%. CONCLUSION: The results of this study suggest that patients with oral squamous cell carcinoma on immunosuppression therapy show progression of cervical lymph node metastasis and extracapsular spread and are at high risk of developing distant metastases.

Pollen Food Allergy Syndrome Caused by Japanese Radish: A Case Report.

Pollen food allergy syndrome (PFAS) is a food allergy that manifests as hypersensitivity symptoms of the oropharyngeal mucosa on ingesting specific foods, and findings resemble herpetic gingivostomatitis. Few reports of PFAS caused by consuming radishes are found in the literature. A 31-year-old man presented to our department with stomatitis and pharyngeal pain. He had no history of allergies. Herpetic gingivostomatitis was suspected. He was admitted to the emergency room a few days later complaining of oral and epigastric pain. Symptoms were similar to those reported previously. He reported frequently consuming raw Japanese radish (Raphans sativus L.) which gave rise to his symptoms. Japanese radish was suspected as the allergen. The skin-prick test confirmed the diagnosis of PFAS. PFAS can be diagnosed easily once the food-causing symptoms are identified. Upon encountering widespread erosion in the oral cavity, it is essential to consider PFAS as the possible cause.

Personal immune profiles: Diversity and prognostic value for oral tongue squamous cell carcinoma evaluated by comprehensive immune parameter analyses with multiplex immunofluorescence.

OBJECTIVES: Understanding the tumor immune microenvironment is becoming increasingly necessary for risk prediction and treatment selection. In particular, oral cancer has various immunosuppressive characteristics in the tumor microenvironment. Therefore, we comprehensively assessed the immune profiles of oral tongue squamous cell carcinoma (OTSCC). MATERIALS AND METHODS: Multiplex immunofluorescence and tissue imaging analyses were performed to evaluate immune profiles at the invasive tumor front of 60 OTSCC surgical specimens. We analyzed 58 immune parameters including the density and proportion (%) of total leukocytes (Leu) and T cells, six subsets of T and myeloid cells, and the expression of programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1). RESULTS: The density, proportion, and location of CD45+ Leu, three T cell subsets (CD8+, Foxp3-CD4+ conventional, and Foxp3+CD4+ regulatory T cells), CD163-CD68+ M1 and CD163+CD68+ M2 macrophages, and neutrophils were highly variable at the individual level. The density and proportion of M2 macrophages were significantly lower in the T1 stage group. Risk prediction analyses for recurrence and/or metastasis (R/M) showed that R/M (+) T1 cases had significantly higher M2 density and percentages. CONCLUSIONS: The immune profiles of OTSCC patients are diverse and cannot be predicted from clinicopathological information alone. The M2 macrophage abundance is a potential candidate biomarker for R/M in the early stage of OTSCC. Personal immune profiling may provide beneficial information for risk prediction and treatment selection.

B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance.

T-cell tolerance is the central program that prevents harmful immune responses against self-antigens, in which inhibitory PD-1 signal given by B7-H1 interaction plays an important role. Recent studies demonstrated that B7-H1 binds CD80 besides PD-1, and B7-H1/CD80 interaction also delivers inhibitory signals in T cells. However, a role of B7-H1/CD80 signals in regulation of T-cell tolerance has yet to be explored. We report here that attenuation of B7-H1/CD80 signals by treatment with anti-B7-H1 monoclonal antibody, which specifically blocks B7-H1/CD80 but not B7-H1/PD-1, enhanced T-cell expansion and prevented T-cell anergy induction. In addition, B7-H1/CD80 blockade restored Ag responsiveness in the previously anergized T cells. Experiments using B7-H1 or CD80-deficient T cells indicated that an inhibitory signal through CD80, but not B7-H1, on T cells is responsible in part for these effects. Consistently, CD80 expression was detected on anergic T cells and further up-regulated when they were re-exposed to the antigen (Ag). Finally, blockade of B7-H1/CD80 interaction prevented oral tolerance induction and restored T-cell responsiveness to Ag previously tolerized by oral administration. Taken together, our findings demonstrate that the B7-H1/CD80 pathway is a crucial regulator in the induction and maintenance of T-cell tolerance.

Keratinocyte-associated B7-H1 directly regulates cutaneous effector CD8+ T cell responses.

Keratinocytes (KCs) may play important roles for maintenance of peripheral tolerance in the upper layers of the skin. Coinhibitory signals mediated via the programmed death (PD)-1 and its ligand B7-H1 (PD-L1/CD274) are crucial for the downregulation of T cell immune responses and for the maintenance of peripheral tolerance. In this study, to investigate the role of KC-expressed B7-H1 in the regulation of T cell immune responses, we generated transgenic (tg) mice overexpressing B7-H1 under the control of keratin 14 (K14) promoter (K14-B7-H1 tg). K14-B7-H1 tg mice displayed impaired contact hypersensitivity (CH) responses to primary and secondary hapten challenges. The K14-B7-H1 tg mice did not exhibit substantial impairment of cutaneous dendritic cell migration after sensitization and of hapten-specific proliferation and IFN-gamma production of CD4(+) and CD8(+) T cells in the draining lymph nodes, suggesting that overexpression of B7-H1 on KCs did not affect the induction phase of the CH response. The systemic or s.c. injection of hapten-sensitized T cells into the K14-B7-H1 tg mice did not efficiently induce the CH response. IFN-gamma expression and apoptosis of KCs in the challenged ears were impaired in K14-B7-H1 tg mice. IFN-gamma production by presensitized CD8(+) T cells stimulated with hapten-pulsed KCs was markedly impaired for the KCs obtained from the K14-B7-H1 tg mice but was restored by the addition of an anti-B7-H1 mAb. These results suggest that KC-associated B7-H1 directly downregulates the effector function of CD8(+) T cells by associating with PD-1 at local inflammatory sites and that it plays a role in peripheral T cell tolerance against exogenous Ags.

Recurrence patterns of oral leukoplakia after curative surgical resection: important factors that predict the risk of recurrence and malignancy.

BACKGROUND: Oral leukoplakia can be treated using a variety of treatment procedures; however, the lesions recur in many cases irrespective of the treatment procedure used. The rate of recurrence was from 7.7% to 38.1%. This study aims to identify the important factors that can lower the risk of recurrence of oral leukoplakia treated by curative surgical resection. METHODS: The clinical records of 52 patients with oral leukoplakia (53 lesions) who underwent curative surgical resection between 2004 and 2009 were retrospectively analyzed for the rate of recurrence, clinical outcome, epithelial dysplasia, lesion location, and resection margins. RESULTS: The recurrence rate following curative surgical resection was 15.1%, with the most common site being the gingiva. Malignant transformation occurred in a single patient (1.9%). Minimal resection margins (<3 mm) were observed in many patients with recurrent disease, and recurrence was more likely in cases with positive margins (epithelial abnormalities at the resection margins) than in those with negative margins. There was no significant association between recurrence and the degree of epithelial dysplasia. CONCLUSIONS: Our data suggest that surgical resection of oral leukoplakia is curative only if all areas of epithelial abnormalities are identified and resected. Moreover, an adequate resection margin may reduce the risk of recurrence.

Oral lichenoid contact lesions related to dental metal allergy may resolve after allergen removal.

Background/ purpose: Distinguishing oral lichenoid contact lesions (OLCLs) from oral lichen planus (OLP) is challenging. This study aimed to identify clinicopathological findings to distinguish OLCLs from OLP, and to evaluate the effectiveness of removing metal allergens in the treatment of OLCLs. Materials and methods: This study retrospectively evaluated 30 patients diagnosed with OLCLs, and 30 age- and sex-matched OLP patients. We also evaluated the effectiveness of removing dental metal containing positive metal allergen, confirmed by skin patch test and metal component analysis in patients with OLCLs. Results: Palladium and gold were the most common patch test-positive metals observed in the oral cavity of patients with OLCLs. The patients with OLCLs were more likely to present with white type lesions in the buccal mucosa and gingiva than were the patients with OLP (p = 0.030, 0.009, respectively). Overall, 50.0% of patients with OLCLs failed to meet the histopathological diagnostic criteria of OLP. Twenty-three of 24 (95.8%) patients with OLCLs showed a complete or partial improvement after the removal of dental metal. Conclusion: The present findings suggest the importance of a skin patch test and metal component analysis to confirm suspected OLCLs related to dental metal allergy, as these lesions may improve with the removal of the allergy-inducing metal.

Fixed Drug Eruption Associated with Nonsteroidal Anti-Inflammatory Drugs for Menstrual Pain: A Case Report.

Fixed drug eruption (FDE) is a type of drug reaction in which cutaneous or mucocutaneous lesions recur at the same site due to repeated administration of the causative drug. The most reported FDE-inducing drugs are nonsteroidal anti-inflammatory drugs (NSAIDs). We report a case of FDE associated with the use of NSAIDs for menstrual pain. A 33-year-old woman was referred to our department with blisters and soreness on her lips, tongue, and labial mucosa. The results of blood examination helped rule out herpes simplex virus infection, pemphigus, and pemphigoid. An FDE was suspected because these symptoms coincided with the use of NSAIDs for menstrual pain. Thus, the patient was advised not to use these NSAIDs but to use acetaminophen instead. No recurrence has been observed since the patient began avoiding these NSAIDs.

High expression of Sam68 contributes to metastasis by regulating vimentin expression and a motile phenotype in oral squamous cell carcinoma.

The present study aimed to investigate the clinical and biological significance of Src­associated in mitosis 68 kDa (Sam68) in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis was performed on tissue samples obtained from 77 patients with OSCC. Univariate analysis revealed that the high expression of Sam68 was significantly correlated with advanced pathological T stage (P=0.01), positive lymphovascular invasion (P=0.01), and pathological cervical lymph node metastasis (P<0.01). Moreover, multivariate analysis demonstrated that the high expression of Sam68 was an independent predictive factor for cervical lymph node metastasis (odds ratio, 4.39; 95% confidence interval, 1.49­14.23; P<0.01). These results indicated that high Sam68 expression contributed to tumor progression, especially cervical lymph node metastasis, in OSCC. mRNA sequencing was also performed to assess the changes in the transcriptome between OSCC cells with Sam68 knockdown and control cells with the aim of elucidating the biological roles of Sam68. Gene Ontology enrichment analysis revealed that downregulated differentially expressed genes (DEGs) were concentrated in some biological processes related to epithelial­mesenchymal transition. Among these DEGs, it was established that vimentin was particularly downregulated in these cells. It was also confirmed that Sam68 knockdown reduced the motility of OSCC cells. Furthermore, the immunohistochemical study of vimentin identified the association between vimentin expression and Sam68 expression as well as cervical lymph node metastasis. In conclusion, the present study suggested that the high expression of Sam68 may contribute to metastasis by regulating vimentin expression and a motile mesenchymal phenotype in OSCC.

Retrospective analysis of schwannoma in the oral and maxillofacial region: clinicopathological characteristics and specific pathology of ancient change.

Schwannomas are benign tumours that originate from the Schwann cells of the nerve. Despite the frequency of their occurrence in the head and neck, data relating to their clinicopathological features in the region are limited. This study reviews the clinicopathological characteristics and specific pathology of ancient (degenerative) change in 40 cases in the oral and maxillofacial region. Medical records were reviewed of the 40 cases treated at Tokyo Medical and Dental University Hospital Faculty of Dentistry between 2000 and 2020. The most frequently involved site was the tongue, and the average tumour size was 13.2 mm. Degenerative changes were observed in eight cases. All tumours were completely excised through biopsy or local excision, and no recurrence was observed on clinical follow up. Statistical analyses revealed significant associations (p < 0.05) between ancient change and tumour size, and between ancient change and the apparent diffusion coefficient (ADC) value derived from diffusion-weighted magnetic resonance imaging (MRI). Analysis suggests that schwannoma progresses over a long period and subsequently undergoes secondary ancient changes. Pathological events such as cystic formation and haemorrhage that are associated with ancient changes, cause hypocellularity and lead to high ADC values. These values may indicate ancient change and should be considered when distinguishing schwannoma from other lesions.

Mandibular Reconstruction with Scapular Systems: A Single-Center Case Series Involving 208 Flaps.

BACKGROUND: The scapular flap is the most versatile composite flap used for mandibular reconstruction. The purpose of this study was to review and summarize findings of cases of mandibular reconstruction with a scapular flap and describe associated outcomes and complications. METHODS: A total of 208 microvascular scapular free flaps were performed for mandibular reconstruction in a total of 205 patients from 2003 to 2018. This study involved a retrospective review of all eligible patients' medical records. RESULTS: There were seven cases (3.4 percent) of microvascular thrombosis. Postoperative bone union was achieved by 201 patients, except for five with total flap necrosis and two with partial flap necrosis. There were four cases (1.9 percent) of mandibular condyle dislocation. Two major types of complications were observed at the donor site, including four cases of infection and six cases of scapular body fracture. Postoperative denture prosthesis was introduced to 97 patients (47.3 percent). Implant treatment was performed in 10 patients (4.9 percent). Functional and aesthetic outcomes were good to excellent. CONCLUSIONS: The scapular composite free flap for mandibular reconstruction was associated with favorable outcomes and demonstrated satisfactory results. Although scapular bone fracture is rare, patients who have undergone mandibular reconstruction using a scapular flap should be monitored for its presence. . CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Oral granuloma in a pediatric patient with chronic graft-versus-host disease: A case report.

BACKGROUND: Oral mucositis is often observed with graft-versus-host disease (GVHD); however, the occurrence of oral granuloma is rare. The rapid increase in granulomatous lesions should be distinguished from malignant tumors in patients with GVHD because malignant diseases can develop in those patients. This case is the youngest pediatric patient with granuloma associated with GVHD. CASE SUMMARY: The patient was a 1-year and 5-mo-old girl who presented to our department for the management of oral nodules. At the age of 5 mo, she was diagnosed with primary immunodeficiency disease, cord blood transplant was performed at 11 mo and bone marrow transplant at 1 year of age. After transplantation, GVHD and oral mucositis developed, and tacrolimus was administered. Interestingly, nodules appeared on the lower lip and buccal mucosa, which spontaneously disappeared. Then, a new nodule appeared on the left lateral border of the tongue. Resection was performed and the histopathological diagnosis was granuloma. The origin of these nodules were considered to be the fibroblasts activated under inflammation caused by GVHD because the calcineurin inhibitor tacrolimus acted on their proliferation. CONCLUSION: It is very important to distinguish oral granulomatous lesions from malignancies if GVHD is present at the base and if immunosuppressive agents and steroids are being administered.

Detection of extraoral primary cancers by positron emission tomography/computed tomography in patients with oral squamous cell carcinoma.

OBJECTIVE: Extraoral primary cancers (EPCs) can appear in patients with oral cancer. This study investigated the use of positron emission tomography/computed tomography (PET/CT) to detect EPCs and to identify characteristics of these cancers. The disease-specific survival rate and the overall survival rate were calculated. STUDY DESIGN: We studied records for 891 patients with oral cancer who underwent PET/CT between January 2006 and December 2016 for the detection of EPCs. RESULTS: A total of 35 EPCs were detected by PET/CT in 34 patients with primary oral carcinoma (3.8%). Of this total, 33 patients had 1 EPC and 1 patient had 2 EPCs. The extraoral lesions were found in the upper gastrointestinal tract (11), colon (6), lung (5), kidney (3), liver (2), prostate (2), breast (2), bladder (1), thyroid (1), pancreas (1), and hypopharynx (1). The disease-specific survival rate was 84.8% and the overall survival rate was 64.6%. CONCLUSIONS: PET/CT was useful for early detection of EPCs. The use of PET/CT for the early detection and treatment of EPCs with no symptoms can improve treatment outcomes.

Leucocyte-associated immunoglobulin-like receptor-1 is an inhibitory regulator of contact hypersensitivity.

Leucocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a membrane receptor of the immunoglobulin (Ig) superfamily that is expressed on most types of haematopoietic cells, and delivers inhibitory signals through interacting with collagens. In order to elucidate the immunological functions of LAIR-1 in vivo, we established transgenic mice expressing a chimeric protein composed of the extracellular domain of LAIR-1 fused with an Ig tag (LAIR-1-Ig), which acts as a decoy by competing with endogenous LAIR-1. The transgenic mice showed an increased susceptibility for development of contact hypersensitivity (CHS), an experimental model of allergic contact dermatitis, in association with enhanced hapten-specific T-cell responses. When T cells from the hapten-sensitized donor mice were transferred into non-sensitized recipients, treatment of either donor mice or recipient mice with LAIR-1-Ig protein accelerated CHS, suggesting a potentially negative role of LAIR-1 in both the sensitization and the elicitation of hapten-reactive T cells. In vitro assays revealed that LAIR-1 decreased the production of interleukin-6 and interleukin-12 in dendritic cells, and inhibited the proliferation and cytokine production of naïve and memory T cells along with G(0)/G(1) cell cycle arrest. Collectively, our findings suggest that LAIR-1 plays a crucial inhibitory role in CHS by regulating antigen-presenting cell and T-cell functions.

Diagnosis and treatment of oral focal mucinosis: a case series.

BACKGROUND: Oral focal mucinosis, the oral counterpart of cutaneous focal mucinosis, is a rare disease. As it has no characteristic clinical or radiological features, diagnosis is established by histopathological and immunohistological examination. We present three cases of oral focal mucinosis occurring in the retromolar (which is extremely rare) and gingival regions. CASE PRESENTATION: Case 1 involved a 26-year-old Japanese man with radiolucency in the right retromolar region on panoramic radiograph and computed tomography; no obvious protrusion was observed in the region. This finding was clinically diagnosed as a tumor of the retromolar region. Case 2 involved a 60-year-old Japanese woman. A tumor-like mass of tissue was identified on the buccal gingiva at the maxillary right canine and first premolar region. The lesion measured 7 × 6 mm and exhibited elastic hardness and healthy-colored mucosa. The lesion was diagnosed as an epulis. Case 3 involved a 47-year-old Japanese woman. A tumor-like mass of tissue was identified on the buccal gingiva at the maxillary right canine and first premolar region. The lesion measured 10 × 10 mm and exhibited elastic hardness and redness of the surface mucosa. This lesion was also diagnosed as an epulis. Resection was performed in all three cases, and the lesions were histopathologically diagnosed as oral focal mucinosis. Postoperative courses were uneventful and, thus far, there have been no recurrences. CONCLUSIONS: Although it is difficult to diagnose oral focal mucinosis based on clinical symptoms and imaging findings, the disease should be considered a possibility when diagnosing benign oral tumors. We believe that an emphasis on histopathologic study is essential to confirm the clinical suspicion.

Management of retropharyngeal lymph node metastasis in oral cancer.

OBJECTIVES: Retropharyngeal lymph node (RPLN) metastasis is extremely rare, and prognosis is significantly poor in oral cancer. We retrospectively examined the management of RPLN metastases in oral cancer. MATERIALS AND METHODS: A total of 1247 patients with oral cancer were treated at our department from January 2002 and December 2016. Among these patients, 374 (30%) had histologically positive lymph node metastases. Of these, 15 patients (1.2%) were diagnosed with RPLN metastases. We evaluated the diagnostic period, size, recurrence pattern, laterality, treatment, and therapeutic outcomes. The Kaplan-Meier method was used to determine overall survival (OS) among the RPLN metastasis group, cervical lymph node (CLN) metastases group, and treatment methods group for RPLN metastases. RESULTS: One patient had RPLN involvement at the initial treatment, and RPLN involvement in other patients was found subsequently. The mean duration in confirming RPLN metastases was 228 days (range, 50-867 days). Surgical therapy was performed in 5 patients, chemoradiotherapy in 7 patients, and best supported care (BSC) in 3 patients. The cumulative 5-year OS rate for the RPLN metastasis group (n = 15) was 38.1%, compared with the rate of 71.3% for the CLN group (n = 359). Regarding the therapeutic approach for RPLN metastases, OS rates were 80.0% (n = 5) in the surgical therapy group, 28.6% (n = 7) in the chemoradiotherapy group, and 0% (n = 3) in the BSC group. CONCLUSION: Early detection and surgical treatment of RPLN metastases are associated with increased survival rate in oral cancer.

Predominant expression of B7-H1 and its immunoregulatory roles in oral squamous cell carcinoma.

We examined cell surface expression of five B7 costimulatory molecules (B7-H1, B7-DC, B7h, CD80 and CD86) in human oral squamous cell carcinoma (SCC) lines. Most human SCC cell lines expressed various levels of B7-H1 and B7-DC. Their expression was further upregulated by interferon (IFN)-gamma stimulation. Immunohistochemical staining revealed substantial and predominant expression of B7-H1 on human primary oral SCC. A murine SCC line, NR-S1, neither expressed B7-H1 nor B7-DC, but induced B7-H1 by IFN-gamma stimulation in culture and the inoculation in vivo. Although NR-S1 tumors grew progressively in immunocompetent syngeneic mice, the administration of blocking anti-B7-Hl or anti-PD-1 mAb significantly inhibited the tumor growth, suggesting the negative regulation of host immune responses by the PD-1:B7-H1 pathway. Our results demonstrate that B7-H1 is predominantly induced on oral SCC within the B7 family molecules. A successful inhibition of tumor growth by blockade of the PD-1:B7-H1 pathway may implicate a new approach for immunotherapy of oral SCC.