The alternation of peripheral lymphocyte subsets in head and neck carcinoma

Peripheral lymphocyte subsets of 115 patients with head and neck carcinomas were examined by the monoclonal antibody technique. In fresh tumor-bearing, the OKT 4 rate was decreased (P less than 0.01) and the OKT 8 rate was increased (P less than 0.05). Consequently the OKT4/OKT8 ratio was decreased (P less than 0.01) compared with normal healthy individuals. This result shows the abnormality of cellular immunity in carcinoma cases. The OKT4/OKT8 ratio reflected the clinical stages and courses sufficiently and correlated with other immunological parameters. The OKT4/OKT8 ratio is considered to be one of the parameters for elucidating the clinical conditions and immunities of carcinoma patients.     

调节性T细胞在头颈部鳞状细胞癌中的研究进展

头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)是一种侵袭性恶性肿瘤,患有该病的患者大多存在严重的免疫缺陷,现有的研究对于HNSCC与宿主免疫系统之间的复杂相互作用,以及T细胞的调节机制有了更加深入的认识。本综述中,我们梳理了Treg细胞与免疫抑制的关系,Treg细胞在HNSCC肿瘤疾病中发生发展的作用,同时也介绍了Treg免疫疗法的潜力。     

Microsatellite instability in squamous cell carcinoma of the head and neck.

Genomic instability or microsatellite instability (MI) in simple repeated sequences was initially recognised in colonic carcinomas and subsequently in other tumours. MI has been associated with mutations in genes concerned with replication and DNA repair. We investigated 34 microsatellite markers in squamous cell carcinoma of the head and neck (SCCHN). Fifty-six tumours, were studied, of which 25 were investigated with ten or more microsatellite markers. In this study we consider two or more microsatellite alterations in a tumour to be diagnostic of MI. We demonstrated that 7/25 (28%) of the tumours had MI at two or more loci and three of these tumours exhibited evidence of 20 or more loci with MI. No correlations were found between MI and previous treatment, site, histological differentiation, positive nodes at pathology, a history of alcohol intake or survival. MI has been demonstrated in T1N0 stage tumours, indicating that these changes may occur early in the disease process. A negative correlation was found between MI and a history of smoking (P = 0.02). Two or more markers of MI were found in three of four non-smokers compared with one of 13 in the smoking group of patients, which suggests a novel mechanism of carcinogenesis in non-smokers.     

Nivolumab in squamous cell carcinoma of the head and neck

Introduction: The prognosis of recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (HNSCC) after failure of first line chemotherapy is dismal. Until the publication of the results of CheckMate 141, not a single agent provided any survival benefit as a second line treatment for R/M HNSCC.

Areas covered: A comprehensive review of the literature was conducted on the role of nivolumab in HNSCC.

Expert commentary: Nivolumab is approved by the Food and Drug Administration for the treatment of patients based on the results of CheckMate 141 showing an overall survival benefit as compared to standard care (single agent docetaxel, methotrexate, or cetuximab). Of particular interest are immune-related adverse events which should be managed according to published guidelines.     

Cetuximab in squamous cell carcinoma of the head and neck

Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemotherapy and chemoradiotherapy are new alternatives for locally advanced disease, particularly induction chemotherapy for patients with unresectable tumors. In recurrent/metastatic disease and after progression to platin-based regimens, no treatments other than best supportive care are currently available. Most SCCHN tumors overexpress the epidermal growth factor receptor (EGFR). This is a tyrosine kinase membrane receptor and has a clear implication in angiogenesis, tumor progression and resistance to different cancer treatments. Cetuximab is a monoclonal antibody that binds to EGFR and alters the tyrosine kinase-mediated signal transduction pathway. The drug is active in colon cancer and is currently being tested in SCCHN patients. For locally advanced disease, cetuximab/radiotherapy combination has demonstrated a benefit in survival when compared with radiotherapy alone as radical treatment. Cetuximab is an active treatment in platin-refractory patients with recurrent/metastatic disease.     

头颈部鳞癌同步放化疗患者外周血淋巴细胞亚群变化的研究

目的：分析头颈部鳞癌患者放化综合治疗前、后细胞的免疫功能变化,探讨放化综合治疗对头颈部鳞癌患者免疫功能的影响。方法：应用FACS Calibur流式细胞仪对46例头颈部鳞癌患者外周血T淋巴细胞亚群进行检测,并将放射疗前、中、后检测结果进行比较。结果：头颈部鳞癌患者治疗前、中、后的CD3＋、CD4＋、CD8＋、NK细胞无明显变化,B细胞、CD4＋/CD8＋比值在放射治疗前后明显变化（P〈0.05,P〈0.05）。结论：头颈部鳞癌患者治疗前后T、B细胞亚群的检测对判断患者的免疫功能及疗效有参考作用,在同步放化疗期间应用增强免疫治疗有积极意义。     

头颈部鳞癌同步放化疗患者外周血淋巴细胞亚群变化的研究

目的:分析头颈部鳞癌患者放化综合治疗前、后细胞的免疫功能变化,探讨放化综合治疗对头颈部鳞癌患者免疫功能的影响。方法:应用FACS Calibur流式细胞仪对46例头颈部鳞癌患者外周血T淋巴细胞亚群进行检测,并将放射疗前、中、后检测结果进行比较。结果:头颈部鳞癌患者治疗前、中、后的CD3+、CD4+、CD8+、NK细胞无明显变化,B细胞、CD4+/CD8+比值在放射治疗前后明显变化(P<0.05,P<0.05)。结论:头颈部鳞癌患者治疗前后T、B细胞亚群的检测对判断患者的免疫功能及疗效有参考作用,在同步放化疗期间应用增强免疫治疗有积极意义。     

Evidence-based radiation oncology in head and neck squamous cell carcinoma.

BACKGROUND AND PURPOSE: Historically, radiation therapy (RT) has been an available treatment option for patients with early resectable head and neck squamous cell carcinoma (HNSCC) and the sole therapy for those with unresectable or inoperable disease. Recently, four noteworthy strategies have emerged for the improvement of therapeutic outcome in the curative treatment of HNSCC: they include the development of altered fractionation radiotherapy, integration of chemotherapy with radiotherapy, incorporation of intensity-modulated radiotherapy and the introduction of targeted biological therapy. These strategies are briefly reviewed in an effort to help interpret evidence-based data and to facilitate clinical-decision making in a clinical context. MATERIALS AND METHODS: For patients with early stage HNSCC no level 1 study exists in which radiation therapy is compared with conservative surgery for the evaluation of local control or survival. Only evidence from prospective and retrospective cohort studies is available to evaluate the role external radiotherapy and/or brachytherapy currently play in limited disease. For patients with locally advanced HNSCC the recommendations to address the questions about better treatment in resectable and unresectable tumors are based on more than 100 randomized Phase III trials included in six meta-analyses on chemo-radiotherapy and/or altered fractionation. Data from phase II trials and cohort studies help interpret the advances in intensity-modulated radiotherapy. RESULTS: External radiotherapy and/or brachytherapy are crucial treatment options in patients with early stage HNSCC. For patients with locally advanced HNSCC, where outcome with conventional radiotherapy is poor, meta-analyses and collective data showed that loco-regional control may be improved at high level of evidence by altered fractionation radiotherapy, chemo-radiotherapy with concomitant approach or association of selected hypoxic cell radiosensitizer with radiotherapy. For these patients, overall survival may be improved at high level of evidence by concomitant chemo-radiotherapy or hyperfractionated RT delivered with increased total dose. Also EGFR-inhibitors (cetuximab)-radiotherapy strategy offers at a lower level of evidence better loco-regional control and overall survival than radiotherapy alone. Chemo-radiotherapy programs can achieve an improved larynx-function preservation program without the risk of overall survival reduction, for patients with larynx or hypopharynx tumors who are candidates to radical surgery followed by radiotherapy. Recently, strong evidence for an improved outcome for high-risk resected patients has been shown by the use of adjuvant concomitant chemo-radiotherapy. Despite improved results, a higher severe toxicity has been largely evidenced with concomitant chemo-radiotherapy by reducing the gain in the therapeutic index with new treatment strategies. Three-dimensional conformal radiotherapy is the minimal standard of technique in HNSCC: however, as advances are promising, intensity-modulated radiotherapy should be largely implemented. CONCLUSIONS: Stepwise improvements in HNSCC non-surgical therapy have shown favorable impact on loco-regional control and overall survival. However, despite hundreds of clinical trials in patients with advanced disease, there is no absolute consensus about patient selection for altered fractionation regimens, type of chemo-radiotherapy association, radiation or chemotherapy dose schedule. Nevertheless, many well-conducted clinical studies have expanded therapy options besides standard radiotherapy and have contributed to defining the evolving standard of care for patients with HNSCC.     

Re-irradiation for head and neck squamous cell carcinoma

Introduction

Local recurrences after curative treatment have a potential for cure with salvage surgery or with re-irradiation.

CD4+ T helper responses in squamous cell carcinoma of the head and neck

Anti-tumor immunity plays an important role in the development of and protection from malignancy. However, there is a lack of information regarding induction of CD4+ T helper responses in patients with squamous cell carcinoma (SCCHN). To explore anti-tumor immune responses against SCCHN, a permanent cell line, Gun-1 was established from a squamous cell carcinoma of the hypopharynx. In addition to its characterization, we performed mixed lymphocyte-tumor cell cultures (MLTC) using peripheral blood lymphocytes and autologous tumor cells. Furthermore, T cell responses to wild type (wt) p53-derived peptides were assessed. Gun-1 cells overexpressed p53 and were negative for HLA-A2 expression. No tumor-specific or wt p53-specific CD8+ CTL lines could be established from peripheral blood mononuclear cells (PBMCs) of this patient. Autologous tumor-specific HLA-DR-restricted CD4+ T helper clone was obtained by limiting dilutions using bulk populations from MLTC. This clone produced IFN-gamma but not IL-5 in response to autologous tumor cells. In addition, CD4+ T cells were generated from the patient's PBMCs which responded to two HLA-DP5-restricted wt p53-derived peptides. Our results suggest that the immune cells specific for autologous tumor as well as wt p53-derived epitopes are present in the peripheral circulation of this cancer patient. However, helper-type CD4+ T lymphocytes represent the predominant anti-tumor response.     

Docetaxel and squamous cell carcinoma of the head and neck

Chemotherapy in head and neck carcinoma is used as palliative treatment but also as induction treatment or combined treatment with concurrent radiation therapy. Platinum and 5-fluorouracil are the most commonly used cytotoxic agents. Docetaxel is an active drug for treating head and neck carcinoma. For patients with recurrent or metastatic disease, docetaxel could be used either as a second line chemotherapy or a first line for patients who received previously platinum or 5FU. In combination with platinum and 5FU, used as induction chemotherapy the TPF regimen is a very active treatment with an overall response rate of 85 to 90% with a manageable acute toxicity rate. This approach is under investigation in terms of ability to obtain more larynx preservation compared to the standard approach with platinum and 5FU. Docetaxel is a radiosensitizer. Concurrent radiochemotherapy using docetaxel alone is feasible, Trials are needed to define the optimal regimen for combining radiation, platinum and docetaxel.     

Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis

To determine the role of the cysteine proteinase inhibitor cystatin C in the invasive behavior of squamous cell carcinoma of the head and neck (SCCHN), Cystatin C protein level was measured in 82 pairs of primary tumour tissue and adjacent noncancerous mucosa, using the enzyme-linked immunosorbent assay. The median level of cystatin C in tumour tissue was 1.18 times lower than that in corresponding mucosa (P=0.031). In normal mucosa samples, the cystatin C level was influenced by the site of sampling: it was lower in nonlaryngeal tissue samples (oral cavity, oro- or hypopharynx) than in laryngeal samples (P=0.004). The tumour cystatin C level correlated inversely with pN-stage (P=0.047), whereas a trend of lower cystatin C levels was observed in the group with extranodal tumour extension compared to those with no extranodal spread (P=0.069). In univariate analysis, the patients with low tumour cystatin C levels exhibited poor disease-free survival (DFS, P=0.013) and disease-specific survival (DSS, P=0.013). In multivariate analysis, the most powerful predictor of survival was pN-stage (DFS: P=0.040, HR 2.78; DSS: P=0.011, HR 4.36,), followed by the cystatin C level (DFS: P=0.043, HR 0.22; DSS: P=0.067, HR 0.25). When comparing the prognostic strength of cystatin C to that of stefin A, another cysteine proteinase inhibitor, which emerged as the most significant prognosticator for survival in our previous study analysing the same cohort of patients, stefin A proved to be significantly more reliable predictor for both DFS and DSS than cystatin C. Our results indicate that cystatin C is implicated in the invasive behavior of SCCHN, and that there are variations in regulation of proteolytic pathways under nonmalignant conditions, inherent to individual subsites inside the upper aerodigestive tract. The correlation between high cystatin C levels and improved survival concurs with the concept of the protective role of high levels of cysteine proteinase inhibitors in tissue homogenates that has been previously suggested by the survival results in breast and lung carcinoma as well as SCCHN.     

Chemoprevention of squamous cell carcinoma of the head and neck

PURPOSE OF REVIEW: The aim of this article is to summarize progress in understanding of the biology of squamous cell carcinoma of the head and neck and of trials to prevent malignant conversion of oral premalignant lesions and the development of second primary tumors in those already treated for squamous cell carcinoma of the head and neck. RECENT FINDINGS: The understanding of squamous cell carcinoma of the head and neck biology is rapidly evolving. Clinical trials for chemoprevention are involving more diverse regimens, following disappointing results of retinoid monotherapy. In-vitro and animal studies form the rationale for the next generation of studies, employing combination, synergistic treatments. SUMMARY: Based on trial data to date, no recommendation for intervention with a chemopreventive agent can be made. It is clear, however, that smoking cessation is an effective intervention for preventing oral premalignant lesions and second primary tumors. Promising trials are being conducted and designed currently. The future of this area of study will involve rational choice of multidrug regimens based on current understanding of the biology of squamous cell carcinoma of the head and neck.     

C-erbB-2 expression in squamous cell carcinoma of the head and neck.

Seventy-five squamous cell carcinomas of the head and neck were analysed for c-erbB-2 expression using immunohistochemical techniques with four different c-erbB-2 antibodies. No membrane staining was seen in any of the squamous cell carcinomas studied with any of the antibodies; however, c-erbB-2 cytoplasmic staining was seen in 60 per cent of the tumours. The significance of cytoplasmic staining is discussed and that it may possibly represent elevated c-erbB-2 expression in squamous cell carcinomas. C-erbB-2 cytoplasmic staining was also observed in 10 of 23 normal specimens obtained from the resection margin of the tumours. No correlations were found between positive c-erbB-2 cytoplasmic staining and any of the clinicopathological parameters or survival.