We previously reported an HLA-A24-restricted cytotoxic T-cell epitope, Survivin-2B80-88, derived from a splice variant of survivin, survivin-2B. In this report, we show a novel HLA-A24-restricted ...T-cell epitope, Survivin-C58, derived from a wild type survivin, and compared their immunogenicity in oral cancer patients.
By stimulating peripheral blood lymphocytes of HLA-A24-positive cancer patients with Survivin-C58 peptide in vitro, the peptide-specific CTLs were induced. In order to compare the immunogenic potential between C58 peptide and 2B80-88 peptide, peripheral blood T-cells from thirteen HLA-A24-positive oral cancer patients were stimulated with either or both of these two peptides.
Survivin-2B80-88 peptide-specific CTLs were induced from four patients, and C58 peptide-specific CTLs were induced from three out of eight patients with over stage II progression. The CTLs exerted cytotoxicity against HLA-A24-positive tumor cells. In contrast, CTL induction failed from a healthy volunteer and all four patients with cancer stage I.
It was indicated that a splicing variant-derived peptide and wild type survivin-derived peptide might have a comparable potency of CTL induction, and survivin targeting immunotherapy using survivin-2B80-88 and C58 peptide cocktail should be suitable for HLA-A24+ oral cancer patients.
Facial asymmetry, which is often due to asymmetry of the mandible, is a naturally occurring phenomenon in patients with hemifacial microsomia (HFM). Only a few attempts have been made to develop ...specific quantitative diagnostic criteria for the mandibular asymmetry of HFM. This pilot study was designed to determine the soft-tissue and skeletal characteristics of patients perceived to have HFM and the factors affecting objective assessment of mandibular asymmetry.
Frontal facial photographs and frontal cephalograms of twelve patients who had HFM with mandibular asymmetry were analyzed. Landmarks and reference lines were determined on the basis of frontal photographs and cephalographic analysis. Linear measurements of the right and left sides were performed to assess the degree of asymmetry of the mandible. The differences between the affected side and the unaffected side were calculated and analyzed statistically.
Significant differences were found for linear measurements of the gonion distance (GoD), full marginal distance (FMD), external marginal distance (EMD), and gonion-menton distance (Go-MeD) in the hard tissue and sFMD, sEMD, sGo-MeD in the soft tissue but not for the gonion distance in soft tissue (sGoD). The differences in sEMD and EMD were significantly correlated, and represented a valid factor affecting the mandibular asymmetry in soft and hard tissues.
The results of this study suggest that appropriate measurements affecting the outline of the mandible such as sEMD and EMD taken from frontal facial photographs and frontal cephalograms provide a useful, objective means of assessing mandibular asymmetry for patients with HFM.
Traumatic facial nerve paralysis is often caused by nerve damage in the temporal bone, such as that from temporal bone fractures, and very rarely by direct facial nerve injuries resulting from ...stings, cuts, bruises or other damage to areas outside of the temporal bone. We report a case of facial nerve paralysis due to pressure from a small bone fragment from a mandibular condylar fracture in which symptomatic improvement was achieved through surgical treatment. The patient was a 30-year-old woman who was injured during a fall. She visited our department after noticing symptoms the following morning that included malocclusion and abnormalities in the muscles of facial expression such as incomplete eye closure. On presentation, a left-side mandibular condylar fracture and severe left-side facial nerve paralysis were identified. As the likely cause of facial nerve paralysis was not a temporal bone fracture, cuts or bruises, but pressure from a small bone fragment, we performed open reduction and internal fixation (ORIF) surgery. In consideration of the surgical risk to nerves, ORIF surgery was performed using a transoral approach. Antecedent steroid therapy was begun just after hospitalization. Improvements were seen in both the malocclusion and facial nerve paralysis. Here we report a case of facial nerve paralysis due to compression from a small bone fragment from a condylar fracture that was treated with ORIF surgery through a transoral approach performed as decompression surgery with a favorable outcome.
Background
The presence of tumor‐infiltrating lymphocytes (TILs) is associated with improved survival in head and neck squamous cell carcinoma. However, the prognostic value of TILs remains unclear ...in oral squamous cell carcinoma (OSCC).
Methods
We evaluated the associations between tumor‐infiltrating CD8+ T‐cell density and survival in five distinct compartments in 139 OSCC cases.
Results
There was a significant association between increased tumor‐infiltrating CD8+ T cells and their distribution. High parenchymal CD8+ T‐cell density at the invading tumor edge was associated with improved overall survival (OS) and disease‐specific survival (DSS; P < 0.01 and P < 0.01, respectively). High stromal CD8+ T‐cell density at the tumor periphery was also associated with improved recurrence‐free survival (RFS; P < 0.01). Cox regression analysis revealed that high stromal CD8+ T‐cell density at the tumor periphery and high parenchymal CD8+ T‐cell density at the invading edge were independent prognostic makers (hazard ratio: 0.38 and 0.19, 95% confidence interval, 0.18‐0.80 and 0.05‐0.72, P = 0.01 and 0.01, respectively) for RFS and OS, respectively.
Conclusions
Assessment of CD8+ T cells at the parenchyma of the invading edge and peripheral stroma provides an indicator of tumor recurrence and prognosis.
Assessment of CD8+ T cells at the parenchyma of the invading edge and peripheral stroma provides an indicator of tumor recurrence and prognosis.
Although immune checkpoint inhibitors (ICIs) are approved for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), the response to ICIs remains unclear.
To ...summarize the clinical outcomes of patients with HNSCC treated with nivolumab (Nivo) in our institution, and provide a basis for research on biomarkers that can predict the efficacy of ICIs.
Forty-four patients with R/M HNSCC who received Nivo (2017-2022) were retrospectively analysed.
Despite the older age of this cohort (median age of 72 years), we observed favourable long-term outcomes, with an overall survival of 24.1 months, which could be attributed to our aggressive nutritional intervention. Older age, poor performance status (≥1), and higher Glasgow Prognostic Scores, reflecting the chronic inflammation and malnutrition of patients, were associated with poor prognoses, with hazard ratios for death of 2.63 (95% confidence interval CI; 1.07-6.46,
= .016), 3.50 (95% CI; 1.28-9.55,
= .001), and 2.69 (95% CI; 1.17-6.21,
= .029), respectively. Peripheral blood biomarker analysis revealed that systemic inflammation may negatively affect the efficacy of Nivo.
Our results suggest that nutrition and inflammation must be the focus of future studies aiming to identify novel biomarkers.
Background/Aim: The role of tumour-infiltrating CD45Ro+ T-cells in oral squamous cell carcinoma (OSCC) is unclear. This study aimed to evaluate prognostic biomarkers for OSCC. Patients and Methods: ...We determined the density of tumour-infiltrating CD45Ro+ T cells in the parenchyma and stroma at the tumour centre (TCe) and invasive front (IF) and examined the association between the density of these cells and histopathological status in 142 patients. Results: Five-year overall survival (OS) and recurrence-free survival were favourable in patients with high CD45Ro+ T-cell density in the TCe stroma. OS was favourable in patients with high CD45Ro+ T-cell density in the IF stroma. Stepwise Cox regression model analysis indicated that CD45Ro+ T-cells in the stroma of the IF and TCe were an independent prognostic factor for OS. Conclusion: CD45Ro+ T-cells in the stroma of the IF and TCe play a role in cancer immune surveillance and may be a useful prognostic factor.
The mortality rate of oral cancer has not improved over the past three decades despite remarkable advances in cancer therapies. Oral cancers contain a subpopulation of cancer stem cells (CSCs) that ...share characteristics associated with normal stem cells, including self‐renewal and multi‐differentiation potential. CSCs are tumorigenic, play a critical role in cancer infiltration, recurrence, and distant metastasis, and significantly contribute to drug resistance to current therapeutic strategies, including immunotherapy. Cytotoxic CD8+ T lymphocytes (CTLs) are key immune cells that effectively recognize peptide antigens presented by the major histocompatibility complex class I molecules. Increasing evidence suggests that cancer antigen‐specific targeting by CTLs effectively regulates CSCs that drive cancer progression. In this study, we utilized data from public domains and performed various bioassays on human oral squamous cell carcinoma clinical samples and cell lines, including HSC‐2 and HSC‐3, to investigate the potential role of olfactory receptor family 7 subfamily C member 1 (OR7C1), a seven transmembrane G‐protein‐coupled olfactory receptor that is also expressed in nonolfactory tissues and was previously reported as a novel marker and target of colon cancer initiating cell‐targeted immunotherapy, in CSC‐targeted treatment against oral cancer. We found that the OR7C1 gene was expressed only in oral CSCs, and that CTLs reacted with human leukocyte antigen‐A24‐restricted OR7C1 oral CSC‐specific peptides. Taken together, our findings suggest that OR7C1 represents a novel target for potent CSC‐targeted immunotherapy in oral cancer.
OR7C1 was found to be preferentially expressed in oral cancer stem cells (CSCs). OR7C1‐specific cytotoxic CD8+ T lymphocyte (CTL) clones could recognize HLA‐A24+ and OR7C1+ oral cancer cells and specifically lyse oral CSCs. The results indicate that OR7C1 is a reasonable candidate for treatment‐resistant CSC.
Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has ...revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy.
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