Impaired general cell-mediated immune functions in vivo and in vitro in patients with nasopharyngeal carcinoma

General cell-mediated immune (CMI) functions in NPC patients were investigated by the in vitro Mantoux and in vitro lymphocyte response to PHA assays. Thirty-eight (50%) of 76 untreated NPC patients were hyporesponsive in the Mantoux assay compared to 27 (25%) of 110 control patients. Forty-three (65.2%) of 66 untreated NPC patients also showed lymphocyte hyporesponsiveness to PHA compared to 15 (15.5%) of 97 control patients. Combined deficiencies were observed in 35 (42.2%) of 83 NPC patients compared to only 2 (3.3%) of 61 control patients. No difference in the frequency of immuno-deficiency was observed between “early” and “late” disease patients. CMI functions of treated “remission” NPC patients were found to be impaired to the same extent as those of untreated NPC patients.     

Impaired cell-mediated immunity in patients with cancer.

The ability of peripheral blood lymphocytes to respond in vitro to phytohemagglutinin (PHA) and to allogeneic cells in mixed leukocyte reaction (MLC) was studied in 85 patients with cancer and in 50 healthy controls. The effect produced by sera from cancer patients on in vitro lymphocyte blastogenesis was tested on autologous cells and on homologous cells from a constant panel of 10 normal volunteers. Patients with cancer showed a distinct deficiency of cellular immune responsiveness reflected in a stage-related impairment of PHA and MLC reactivity. This deficiency seems at least partially attributable to the presence of lymphocyte depressive factors in cancer sera, since such sera reduced the reactivity of both autologous and normal homologous lymphocytes to a level that was significantly lower than that found in the presence of pooled normal serum. The inhibitory activity of cancer sera was directly related to the extent of the neoplasia.     

Impaired long-term T cell immunity to Epstein-Barr virus in patients with nasopharyngeal carcinoma.

The long-term T cell immunity to Epstein-Barr virus (EBV) is considered to play an important role in suppressing proliferation of EBV-infected B cells and outgrowth of EBV-associated tumors. It can be manifested and quantified by the EBV-induced focus regression assay. In the present study, we examined the strength of T cell immunity to EBV in patients with nasopharyngeal carcinoma (NPC) and other cancers originating from the head and neck region. In contrast to patients with other types of cancers, including EBV-negative NPC, patients with EBV-positive NPC were found to have a profound impairment in the long-term T cell immunity to EBV.     

Familial nasopharyngeal carcinoma in patients who are not Chinese.

BACKGROUND. Nasopharyngeal carcinoma (NPC) is a malignancy that is prominent in Cantonese Chinese people. It is presumed to result from an interaction of genetic and environmental factors, including the Epstein-Barr virus (EBV). In an attempt to further clarify the pathogenesis of this disease, an evaluation of NPC occurring in racial/ethnic groups not considered susceptible to this disease could be informative. METHODS. A white family with NPC occurring in three siblings was investigated and information was gleaned from literature on other reports of familial NPC in non-Chinese families. RESULTS. In the family being investigated, another genetically determined disease, hemophilia, was identified. Radiation early in life was noted to be a possible risk factor for NPC in the proband. A review of familial NPC in the white population revealed that in contrast to sporadic NPC, which is usually of the well-differentiated type, familial NPC usually is poorly differentiated. CONCLUSIONS. Familial NPC offers an important opportunity to investigate the etiology of this disease. With newer laboratory techniques to investigate pathogenetic mechanisms, detailed evaluations of non-Chinese NPC families may become increasingly important.     

Cell-mediated immunity, Epstein-Barr virus and nasopharyngeal carcinoma.

Cellular immunity is apparently important in host defenses against cancer. A growing body of information on CMI to EBV is here reviewed, providing a strong basis for studies of such reactivity in NPC. Present work suggests that CMI responses to virus- and tumour-associated antigens may have implications for etiology, diagnosis and treatment.     

In vivo induction of dendritic cell-mediated cytotoxicity against allogeneic pancreatic carcinoma cells

The objective of this study was to assess the toxicity and immunological response induced by autologous dendritic cells (DCs) pulsed with allogeneic tumor lysate in a pancreatic cancer patient. The lack of available tumor peptides in pancreatic cancer strongly supports the idea to use allogeneic tumor cells as a source of antigens. The patient suffering from a stage IV pancreatic cancer received 1-2x10(7) autologous monocyte-derived DCs in three-week intervals injected into a groin lymph node. Monocytes from peripheral blood were isolated by magnetic bead selection. For the first ten vaccinations DCs were loaded with autologous tumor cell lysate obtained during surgical exploration. After consumption of the autologous lysate, equal numbers of DCs were pulsed with lysate of the tumor cell line AsPc-1 and BxPc-3 for a further five vaccinations. Peripheral mononuclear cells (PMNCs) were harvested after the seventh and compared with PMNCs obtained after the fourteenth vaccination for immunological response. Delayed type hypersensitivity reactivity to DCs pulsed with autologous and allogeneic tumor lysate was also assessed. The patient received a total of fifteen vaccinations. There was no toxicity or evidence of autoimmunity observed. Delayed type hypersensitivity was found to be positive for the autologous as well as the allogeneic tumor lysate pulsed DCs. in vitro cytotoxicity assays demonstrated a dramatic increase of the PMNC killing capacity against the pancreatic cancer cell lines AsPc-1 and BxPc-3 after the fourteenth compared to the seventh vaccination. CT scans revealed a stable disease for six months. The administration of autologous DCs pulsed with allogeneic tumor lysate is non-toxic and suitable for inducing an immunological anti-tumor response. Even though this study was confined to a single patient, the data might open a door for novel immunotherapeutical strategies.     

Activated CD4-positive T-lymphocytes and impaired cell-mediated immunity in patients with carcinoma of the urinary bladder with schistosomiasis.

Patients with schistosomiasis of the urinary bladder (SB) associated with carcinoma of the bladder (SCB) or carcinoma of the prostate (SCP) have a variety of immunologic abnormalities, including the presence of HLA-DR+ and interleukin-2 receptor-positive (IL-2R+) T-lymphocytes in circulating blood. This study demonstrated that, the HLA-DR+ and IL-2R+ antigens are selectively expressed on majority of the CD4+ T-lymphocytes of patients with SCB, whereas, these antigens are expressed almost equally on both CD4+ and CD8+ T-lymphocytes of patients with SB and SCP. Expressions of HLA-DR+ and IL-2R+ antigens in CD4+ T-lymphocytes, and a depressed response of this T-cell subset to phytohemagglutinin and Concanavalin A stimulations seems to be the characteristic feature of these patients with SCB. In addition, the autologous mixed lymphocyte reaction (AMLR) and allogenic mixed lymphocyte reaction (MLR) was depressed in patients with SCB. However, patients with SCP demonstrated a normal MLR, even though the AMLR was highly depressed. The immunoregulatory role of the HLA-DR+, IL-2R+, CD4+ helper/inducer T-lymphocytes, and the AMLR and MLR abnormalities we have identified in patients with SCB may be important and could play a role in the pathobiology of these diseases in humans.     

Particular features of cell-mediated immunity in patients with anaplastic gliomas

Summary The authors studied 24 patients affected by anaplastic gliomas in regard to the killer (Antibody-Dependent Cellular Cytotoxicity) and natural killer (Spontaneous Lymphocyte-Mediated Cytotoxicity)immunological functions, by counting the Cr⁵¹ release in Chang liver and K 562 cell cultures, respectively. These parameters were also evaluated in 24 healthy donors as control, in 24 patients affected by bladder cancer and in nine cases of kidney cancer.Our data show, pre-operatively, a statistically significant impairment of ADCC and SLMC activity in glioma patients as compared both with controls, bladder and kidney cancer patients.The particular impairment of K and NK functions in gliomas is discussed with regard to the specific features of Central Nervous System malignancies. An improvement of ADCC activity was also found in the post-operative samples. This finding confirms other reports about partial restoring of altered immunocompetence after surgery, suggesting a link between extention of tumor mass and impaired immunological reactions.     

初治鼻咽癌患者的细胞免疫功能和检测指标的评价

目的检测初治鼻咽癌患者疗前的多项细胞免疫指标,判断其细胞免疫功能状态,比较不同检测指标的准确性.方法 2003年3月～2003年12月收治鼻咽癌患者105例,疗前抽取晨起空腹外周静脉血,流式细胞术检查其T淋巴细胞亚群、T细胞活化水平、B细胞和NK细胞比例,3H-TdR释放法检测LAK活性,并结合肿瘤的临床分期和乙肝两对半检查,研究各指标之间的相关关系.结果根据1992年福州分期,Ⅰ期6例,Ⅱ期21例,Ⅲ期48例,Ⅳa期30例.所有患者的BUN、Cr均大致正常,且排除HIV感染.CD8与病期有显著相关(r=0.218,P=0.013);与病期有接近显著相关关系的指标有CD4/CD8比值(P=0.051)、CD8 CD25 细胞(P=0.059)和LAK细胞活性(P=0.057).患者的临床病期与HBsAg阳性有显著相关关系(r=0.220,P=0.012).排除HBV因素后与病期有显著相关关系的指标有CD4(r=-0.253,P=0.025)、CD8(r=0.284,P=0.013)、CD4/CD8比值(r=-0.346,P=0.003)、B细胞(r=-0.221,P=0.043)和CD8 CD25 细胞(r=-0.436,P=0.000).结论鼻咽癌初治患者的细胞免疫抑制与临床病期有关,还与HBV感染相关.CD4和CD8细胞百分比及其比值、CD8 CD25 细胞百分比、LAK细胞活性是较敏感的指标.     

Environmental backgrounds of young Chinese nasopharyngeal carcinoma patients

Twenty-four Chinese NPC patients under 25 years of age at the time of diagnosis were interviewed. The interviews were carried out in the presence of their families in 22 cases and concentrated on the environmental background of the subject's infancy and early childhood. An analysis of the results eliminated household inhalants, aerial contaminants, medicines, food therapy, spices, fresh foods and soya sauce as likely factors in carcinogenesis. The only remaining foods eaten by all subjects and worthy of consideration were laap cheung, salted fish and tau si. Salted fish was the most commonly eaten and the only one fed to babies. In childhood, the subjects had rarely or never been fed vegetables or fruits. Most had, since childhood, been characteristically sickly, inactive, withdrawn and choosy about their food. It would appear that consumption of salted fish and vitamin C-deficiency in early childhood are important environmental factors and that a certain personality type may be associated with an increased risk.     

Soluble interleukin-2 receptors in patients with nasopharyngeal carcinoma.

The authors performed a retrospective analysis of serum soluble interleukin-2 receptor (sIL-2R) levels in 72 patients with nasopharyngeal carcinoma (NPC) using an enzyme immunoassay. Their objectives were to determine the value of serum sIL-2R in estimating the tumor burden, and its predictive value in response to therapy and prognosis. The data showed that serum sIL-2R levels in patients were significantly higher than that of healthy controls. The serum levels correlated with clinical staging and hence the tumor burden of NPC. Serial measurement of serum sIL-2R provided an accurate prognostic index of the clinical response to radiotherapy in at least 89% of patients with raised serum sIL-2R at initial diagnosis (defined as mean + 2 SD of healthy controls) and a reliable predictive index in all patients who subsequently developed distant metastasis despite initial radiotherapy. Simultaneous measurement of Epstein-Barr virus-related serology (IgA-VCA and IgG-EA) failed to demonstrate predictive value comparable with that of serum sIL-2R. The authors conclude that monitoring serum sIL-2R levels has clinical and prognostic significance in patients with NPC and that prospective studies are indicated.     

Changes in cell-mediated immunity in patients undergoing radiotherapy

The cell-mediated immune status of 147 patients who received radiotherapy was evaluated using in vitro tests (PHA, E-rosette and spontaneous blastogenesis) both before and 6 weeks after the end of radiation. All patients had verified malignancies, involving the bronchus in 29 cases, breast in 28, female genital system in 26, head and neck in 20 and bladder in 15. Patients suffering from bronchogenic carcinomas or malignancies of the head and neck showed a relative high degree of immune suppression. Our findings indicate a trend towards some improvement in PHA reactivity, as well as in as the percentage of E-rosette-forming cells after treatment, which is more noticeable in patients with pelvic or breast tumors. A relationship seems to exist between the tumor load and the immune status, which reverts to a normal pattern when the former is extinguished. Moreover, patients with poor clinical response display a profoundly depressed level of immune status without any improvement after treatment.     

Prognostic impact of family history in southern Chinese patients with undifferentiated nasopharyngeal carcinoma

Background:

Family history of cancer is associated with developing nasopharyngeal carcinoma (NPC); however, the impact of it on survival among established NPC patients remains unknown.

Methods:

We retrospectively analysed 1773 southern Chinese patients. Associations between a first-degree family history of NPC and overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were estimated by Cox regression.

Results:

Among 1773 patients, 207 (11.7%) reported a first-degree family history of NPC. Compared with patients without a family history, the adjusted hazard ratios among those with it were 0.60 (95% confidence interval (CI), 0.37–0.98; P=0.040) for OS, 0.52 (95% CI, 0.24–1.12; P=0.096) for LRFS and 0.51 (95% CI, 0.27–0.97; P=0.040) for DMFS. There were trends for improving OS, LRFS and DMFS with increasing number of affected relatives (P_trend: 0.050, 0.114 and 0.044, respectively). But no significant benefits of family history in second- or third-degree relatives were observed. In subgroup analysis, we observed the effects of family history with restriction to male patients and those of advanced stage and treated with conventional radiotherapy and addition of chemotherapy.

Conclusion:

A first-degree family history of NPC is associated with improved survival of patients.     

鼻咽癌放疗后放射性脑病307例临床特征分析

目的:分析鼻咽癌放疗后放射性脑病的临床特征及危险因素,为临床医生提供放射性脑病发生规律。方法:收集2006-01-2009-12在浙江省肿瘤医院接受放疗的鼻咽癌患者临床资料,分析发生放射性脑病患者的临床特征,进行统计分析。结果:放射性脑病发生在鼻咽癌放疗后4~192个月,中位40个月。接受常规面颈联合野放疗及高剂量照射的患者发生放射性脑病的机会更大,发生率分别为6.6%和4.4%。结论:放射性脑病多数发生在放疗结束后3.5年内,与肿瘤分期、放疗方式以及高剂量照射等有关。     

Natural cell-mediated cytotoxicity in rats. II. In vivo augmentation of NK-cell activity

Natural cell-mediated cytotoxicity in rats as well as in mice has been shown to vary consistently with age, with peak levels detectable at 5-10 weeks. The levels of cell-mediated cytotoxicity against tumor cells could be augmented in strains of inbred rats with either high or low levels of natural reactivity, by IP injection of a variety of agents, including C. parvum, LCMV, KRV, and poly I:C. The specificity of the augmented cytotoxicity appeared to be the same as the specificity of natural killer cells which are found in normal rat spleen cells. Similarly, the cells mediating the augmented cellular cytotoxicity were small, non-adherent, esterase-negative lymphocytes with Fc receptors, as are rat NK cells. The kinetics and organ distribution of the augmentation of NK activity by poly I:C and C. parvum were compared and the kinetics were found to differ, with a shorter time course of augmented activity seen after inoculation with poly I:C. These data indicate that interferon may play a central role in the augmentation of NK activity in vivo.     

Multiple malignant neoplasms in patients with nasopharyngeal carcinoma

The records of 759 patients with nasopharyngeal carcinoma were reviewed. Fifteen of them also suffered from another malignant neoplasm. All patients had histological confirmation of the nasopharyngeal carcinoma and the other malignant neoplasm. There was no predilection for the second malignant neoplasms to arise from the bronchus. Although the observed number of second malignant neoplasms was not significantly different from the expected number (p greater than 0.05) computed by the patient-month approach, in 1 patient the second malignant neoplasm may be causally related to the previous treatment of nasopharyngeal carcinoma by radiotherapy.     

Prognostic value of ABO blood group in southern Chinese patients with established nasopharyngeal carcinoma

Background:

ABO blood group is associated with aetiology of nasopharyngeal carcinoma (NPC); however, the effect of it on survival of patients diagnosed with NPC has not been explored.

Methods:

We retrospectively analysed two cohorts of southern Chinese patients with WHO histological type III: intensity-modulated radiotherapy (IMRT) cohort, 924 patients; and conventional radiotherapy (CRT) cohort, 1193 patients. Associations of ABO blood group with survival were estimated using Cox regression.

Results:

In IMRT cohort, we observed significant associations of blood type A with overall survival (OS) and distant metastasis-free survival (DMFS), compared with type O, after adjusting for prognostic factors. Compared with non-A blood types (B, AB, and O), type A patients had significantly lower OS and DMFS (adjusted hazard ratio (HR)=1.49, 95% CI 1.03–2.17, P=0.036; HR=1.68, 95% CI 1.13–2.51, P=0.011, respectively); similar results were obtained in CRT cohort. Subgroup analyses of the entire population showed that lower OS conferred by blood type A was not significantly modified by age, smoking status, drinking status, immunoglobulin A against Epstein–Barr virus viral capsid antigen (VCA-IgA) titre, or chemotherapy; however, lower OS was not observed in female patients or patients with early clinical stage disease.

Conclusion:

ABO blood group is associated with survival in NPC; patients with blood type A had significantly lower OS and DMFS than patients with non-A blood types.