Association between circulating CD39+CD8+ T cells pre-chemoradiotherapy and prognosis in patients with nasopharyngeal carcinoma / 中华医学杂志(英文版)

BACKGROUND@#The mortality rate among patients with nasopharyngeal carcinoma (NPC) has improved significantly with the advent of chemoradiotherapy strategies. However, distant metastasis remains problematic. Tumor-specific reactivity in cancer patients has been detected exclusively in CD39+ T cells, particularly in CD39+CD103+ T cells. Circulating cancer-specific T cells are important for protecting against metastasis. This study aimed to evaluate the predictive value of circulating CD39+CD8+ T cells for metastasis in patients with NPC.@*METHODS@#We performed a cross-sectional, longitudinal study of 55 patients with newly diagnosed NPC of stage III-IVa. All patients were initially treated with standard combined chemoradiotherapy. Blood samples were obtained from 24 patients before and at 1 month and 6 months after treatment. T cell expression of CD39 and CD103, together with the markers of T cell exhaustion programmed death-1 (PD-1)/T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and markers of cell differentiation CD27/CC-chemokine receptor 7/CD45RA, was examined by flow cytometry. The Wilcoxon rank-sum test analysis was used to analyze the differences between two groups. Kaplan-Meier analysis was used for analysis of progression-free survival (PFS).@*RESULTS@#The expression of circulating CD39+CD8+ and CD39+CD103+ CD8+ T cells was significantly higher in patients without distant metastasis (CD39+CD8+: 6.52% [1.24%, 12.58%] vs. 2.41% [0.58%, 5.31%], Z=-2.073, P=0.038 and CD39+CD103+CD8+: 0.72% [0.26%, 2.05%] vs. 0.26% [0.12%, 0.64%], Z=-2.313, P = 0.021). Most CD39+ T cells did not express PD-1 or Tim-3. Patients with high expression of CD39+CD103+CD8+ T cells had better PFS than patients with low expression (log rank value = 4.854, P = 0.028). CD39+CD8+ T cells were significantly elevated at 1-month post-treatment (10.02% [0.98%, 17.42%] vs. 5.91% [0.61%, 10.23%], Z = -2.943, P = 0.003). The percentage of advanced differentiated CD8+ T cells also increased at 1-month post-treatment compared with pre-treatment (33.10% [21.60%, 43.05%] vs. 21.00% [11.65%, 43.00%], Z = -2.155, P = 0.031). There was a significant correlation between elevated CD39+CD8+ T cells and increased effector memory T cells (intermediate stage: r = 0.469, P = 0.031; advanced stage: r = 0.508, P = 0.019).@*CONCLUSIONS@#CD39+CD8+ circulating T cells have preserved effector function, contributing to an improved prognosis and a reduced risk of metastasis among NPC patients. These cells may thus be a useful predictive marker for a better prognosis in patients with NPC.

Human Leukocyte Antigen-A Allele Distribution in Nasopharyngeal Carcinoma Patients Showing Anti-Melanoma-Associated Antigen A or Synovial Sarcoma X-2 T Cell Response in Blood / 中华医学杂志(英文版)

<p><b>Background</b>Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma (NPC) patients. In this study, we evaluated the T cell response to melanoma-associated antigen (MAGE)-A1, MAGE-A3, or synovial sarcoma X-2 (SSX-2) in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen (HLA)-A types were analyzed to provide evidence of designing novel therapy.</p><p><b>Methods</b>Sixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman's rank correlation was used to analyze the relationship of T cell responses.</p><p><b>Results</b>HLA-A*02:01, A*02:07, and A*24:02 were the three most frequent alleles (18.9%, 12.3%, and 11.5%, respectively) among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/10 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A*02:01 and A*24:02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders.</p><p><b>Conclusion</b>MAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.</p>

HLA-A*02-B*46 haplotype: an adverse prognostic factor in Han patients with nasopharyngeal carcinoma / 华中科技大学学报（医学）（英德文版）

Epidemiological studies have shown that human leukocyte antigen (HLA) allelic polymorphisms are closely correlated to susceptibility to nasopharyngeal carcinoma (NPC), and in a previous study, we showed that HLA-B*46 and HLA-A*02-B*46 haplotypes were strongly associated with NPC susceptibility. In this retrospective study, we investigated the phenotype of the HLA-A and HLA-B alleles and haplotypes and correlated these data to the clinical and pathological parameters of NPC to understand the role of HLA alleles and haplotypes in NPC prognosis. The cohort comprised 117 NPC patients from a Han population in Xinjiang. The local recurrence-free survival (LRFS), distant metastasis- free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were analyzed. The 5-year DMFS of the HLA-A*02-B*46 haplotype carriers and non-carriers was 66.4% and 90.3%, respectively. In addition, age was found to be a prognostic factor for LRFS, DFS, and OS (P=0.032, 0.040, and 0.013, respectively). We found that the HLA-A*02-B*46 haplotype might be a prognostic marker in addition to the traditional TNM staging in patients with NPC.

Associations of Human Leukocyte Antigen-DRB1 Alleles with Nasopharyngeal Carcinoma and Its Clinical Significance in Xinjiang Uyghur Autonomous Region of China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Genetic susceptibility is one of the major etiological factors for nasopharyngeal carcinoma (NPC). Among the genetic predisposing factors, human leukocyte antigen (HLA) genes have been reported to be associated with NPC. This study aimed to investigate the associations of HLA-DRB1 alleles with NPC and the clinical significance of HLA-DRB1 alleles in NPC.</p><p><b>METHODS</b>From January 2009 to December 2013, 140 NPC patients (118 Han patients and 22 Uyghur patients) and 158 healthy controls (81 Han individuals and 77 Uyghur individuals) from Xinjiang Province were genotyped for HLA-DRB1 using the polymerase chain reaction-sequence specific primer technique. Chi-square analysis was used when comparing allele frequencies between groups. The clinical outcomes were evaluated by Kaplan-Meier method and Cox regression model.</p><p><b>RESULTS</b>Compared with healthy controls, the allele frequency of HLA-DRB1*0701 was increased in the Uyghur patients (P = 0.008) but not in the Han patients (P = 0.869). HLA-DRB1*0101 allele was presented with higher frequency in clinical Stage I + II group compared with clinical Stage III + IV group in the Han patients (P = 0.015) but not in the Uyghur patients (P = 1.000). Higher frequency of HLA-DRB1*1501 allele was observed in patients aged <45 years compared with those in patients aged ≥45 years (P = 0.002). Neither HLA-DRB1*0701 nor HLA-DRB1*0101 had a statistically significant association with 3-year survival.</p><p><b>CONCLUSIONS</b>This study found HLA-DRB1*0701 in Uyghur population was associated with an increased risk of developing NPC. In Han population, we found HLA-DRB1*0101 was associated with protection from disease progression, and HLA-DRB1*1501 was associated with early age of onset. HLA-DRB1 could not be identified as a prognostic indicator for NPC in either Han or Uyghur patients.</p>

Spinal cord biological safety comparison of intensity modulated radiotherapy and conventional radiation therapy / 中华放射医学与防护杂志

Objective To compare the spine intensity modulated radiation therapy (IMRT) and the conventional radiation therapy on the beagle spinal cord neurons,in order to prove the biological safety of IMRT of the spinal cord.Methods Twelve selected purebred beagles were randomly divided into 2 groups.A beagle clinical model of tumor was mimiced in the ninth and tenth thoracic vertebrae.Then the beagles were irradiated by 2 different models of intensity modulated radiotherapy and conventional radiation therapy,with the total irradiation doses of 50 and 70 Gy.The samples of spinal cord were taken out from the same position of the nine and tenth thoracic vertebrae at the third month after radiation.All the samples were observed by the electron microscope,and the Fas and HSP70 expression in spinal cord neurons were evaluated by immunohistochemistry method.Terminal deoxynucleatidyl transferase mediated dUTP nick and labeling (TUNEL) technique was used to examine the apoptotic cells in the spinal cord.Results The neurons in the spinal cord of IMRT group were mainly reversible injury,and those in the conventional radiation therapy were mainly apoptosis.Compared with the conventional radiation therapy group [50 Gy group,(7.3±1.1)% ;70 Gy group,(11.3 ±.4)%],the apoptosis rate of the spinal cord neurons of the intensity modulated radiotherapy group[50 Gy group,(1.2 ±0.7)%;70 Gy group(2.5 ±0.8)%] was much lower[(50 Gy group,t＝0.022,P＜0.05;70 Gy group,t＝0.017,P＜0.05)].The expression levels of Fas in the IMPT group(50 Gy group,4.6 ±0.8;70 Gy group,7.4 ±1.1)were also much lowerthan those in the other group(50 Gy group,15.1 4-6.4;70 Gy group,19.3 ±7.6.50 Gy group,t＝0.231,P＜0.05;70 Gy group,t:0.457,P＜0.05),while the expression levels of HSP70 in the IMPT group(50 Gy group,9.1 ±0.8;70 Gy group,7.3±1.4)were much higher than those in the conventional radiation therapy group(50 Gy group,2.1 ±0.9;70 Gy group,1.7±0.3;50 Gy group,t＝0.153,P＜0.05;70 Gy group,t＝0.223,P＜0.05).The expression of Fas/HSP70 was positively correlated with the apoptosis rate of the spinal cord neurons(r＝0.996,t＝1.14.P＜0.05).Conclusions The late radiotherapy response of the spinal cord neurons was obviously observed on the third month.Comparison of the morphology and apoptosis rate of the spinal cord neurons after radiotherapy,the expression of Fas and HSP70 indicated that the biological safety in the 1MRT might be much better than that the conventional radiation therapy.

Effects of modeling IMRT on cell cycle and expression of Cyclin D1/Cyclin B1 in CNE-2 cell lines / 上海第二医科大学学报

0.05).The mRNA expression of Cyclin B1 of IMRT group was significantly higher than that of ART group at each dose point(P