妇科肿瘤患者不同状态下的免疫功能评价

目的:研究妇科肿瘤患者的免疫功能变化情况,观察机体免疫功能与患者年龄、临床分期、治疗方式等因素的关系。方法:运用流式细胞术对151例患者外周血T淋巴细胞亚群及NK细胞进行检测。结果:与良性组比较,恶性肿瘤组CD3+下降 、CD4+下降极显著(P＜0.01), CD4+/CD8+下降显著（P＜0.05）,CD8+则略有升高;恶性肿瘤组CD4+、CD4+/CD8+表现出随临床分期提高逐渐降低的趋势,CD8+则反之。其中Ⅲ-Ⅳ期CD8+、CD4+/CD8+较I期存在极显著性差异（P＜0.01）;与未转移组比较,已转移组CD3+下降、CD4+下降显著(P＜0.05),CD4+/CD8+下降极显著（P＜0.01）,CD8+升高;术后组CD3+、CD4+、CD4+/CD8+较未治疗组升高,CD8+下降,并且CD4+/CD8+升高显著(P＜0.05);术后组CD4+、CD4+/CD8+较放化疗组升高、CD8+下降,差异均极显著（P＜0.01）;放化疗组CD4+、CD8+、CD4+/CD8+与未治疗组比较差异具有统计学意义(P＜0.05)。结论:妇科肿瘤患者的免疫功能受到不同程度的抑制,这种抑制与患者年龄、病情进展存在一定的相关性。在肿瘤治疗中解除瘤负荷和保护机体的免疫功能具有同等重要的意义。     

Circulating immune complexes in patients with malignant neoplasms

Circulating immune complexes were identified in 143 patients with malignant tumors (70--solid cancer, 37--acute leukemia, 21--chronic lympholeukemia and 15--myelomatosis) as well as in 64 patients with chronic inflammatory diseases. Immune complexes were detected in 40% with the aid of precipitation with polyethylene glycol alone and in 50%--by using it in combination with an anticomplementary method. Immune complexes occurred more often in acute myeloid leukemia (66%) than in pancreatic cancer (23%) or chronic lymphoid leukemia (29%). The immunoglobulin profile of complexes varied: in patients with pancreatic cancer, mainly IgM was found; in leukemic patients--different combinations of IgM, IgA and IgG. In the immune complexes of some patients with pancreatic disease, CEA and normal pancreatic antigens were detected.     

The blood and urine concentration of 5-fluorouracil in patients with pancreatic neoplasms]

The kinetics of 5-fluoruracil concentration in blood and urine in 18 patients with cancer of the pancreas was determined in a regional and systemic method of its administration. The concentration of 5-fluoruracil in blood was found to be, as a rule, lower and the time of detection shorted after i/a (regional) administration as compared with i/i (systemic) one. Accordingly, less amount of the substance involved is excreted with the urine in regional chemotherapy. This allows an application of large single and sessional doses in insignificant general toxic effects and also gaining much better therapeutic effect.     

胰腺癌患者的免疫状态

在胰腺癌的发生发展中,患者的全身和肿瘤局部免疫状态均发生了改变,致使肿瘤逃脱机体免疫.这种机制包括全身和肿瘤局部抑制免疫细胞的诱导和相关细胞因子的产生.全身免疫状态的改变包括免疫抑制细胞的出现,T细胞亚群免疫功能的改变,自然杀伤细胞、淋巴因子激活的杀伤细胞功能的抑制等;肿瘤局部免疫状态表现出肿瘤浸润淋巴细胞功能的缺失、Th1/Th2细胞因子失衡等.     

围手术期胶质瘤患者细胞免疫功能的表达

 目的　探讨围手术期胶质瘤患者细胞免疫功能的表达。方法　用免疫荧光技术检测 4 8例胶质瘤患者围手术期T淋巴细胞亚群和NK细胞百分率。结果　胶质瘤患者CD3、CD4 、CD8及CD4 /CD8比值均明显低于对照组 ;肿瘤切除术后细胞免疫功能有所恢复 ,但与术前比较无明显差异 ,且仍低于正常状态。结论　胶质瘤患者细胞免疫功能低下 ,且肿瘤切除术后其细胞免疫功能尚难很快恢复到正常状态 ,临床上应注意围手术期细胞免疫功能的保护。     

Specific cellular immune responses in patients with malignant gliomas.

The leukocyte adherence inhibition assay was used to measure cell-mediated immunity in 26 patients with malignant glial neoplasms and 41 control subjects. A significant inhibition of leukocyte adherence was observed in 21 of 26 (80%) glioma patients in the presence of a 3 M KCl extract of glioma tissue, as compared to that of normal brain extract. Among the control group, no significant difference in the percentage of nonadherent leukocytes was noted in the presence of either antigen. To study the specificity of the reaction, a 3 M KCl extract of meningioma, pituitary tumor, carcinomas of breast, and lung, melanoma, brain, and heart tissues were used as nonspecific antigens. Such studies revealed significantly lower values of nonadherent leukocytes. These data indicate that patients with malignant glial neoplasms manifest a cellular immune response to glioma-associated antigens which can be measured by the tube leukocyte adherence inhibition assay and that leukocyte adherence inhibition assay may render additional useful information in diagnostic and prognostic evaluation of malignant glial neoplasms.     

Local cellular immune reactions in cancer patients

The analysis of 178 cases of stage I-II breast cancer showed morphological features of local cell-mediated immune reactions to be of limited prognostic value. A comparative evaluation of some characteristics of cell surface receptors, such as ability to spontaneous rosette formation with sheep erythrocytes and sensitivity to theophylline, was carried out in lymphocyte samples obtained from tumor tissue and peripheral blood of 76 cancer patients. The said parameters were studied in breast cancer patients with respect to presence or absence of regional metastases. Several patterns of rosette-forming cell reaction to theophylline were identified, the incidence of some of them being determined by the presence or absence of regional metastases. The level and functional activity of surface receptors of tumor mononuclear cells proved to influence prognosis.     

Hypoxanthine concentrations in normal subjects and patients with solid tumors and leukemia

Mean plasma hypoxanthine (Hyp) concentrations determined by high-pressure liquid chromatography were 0.56 microM (range, 0.2 to 1.9 microM) in 16 normal subjects, 0.68 microM (range, 0.1 to 1.1 microM) in 10 untreated acute leukemic subjects, and 0.89 microM (range, 0.3 to 2.6 microM) in 14 solid tumor patients. Despite large differences in Hyp concentration between patients, every 4-hr sampling, indicated that diurnal variation in individual patients was small (maximum, 2.3-fold). While the mean plasma and malignant effusion Hyp concentrations did not differ significantly, bone marrow plasma Hyp concentration averaged 4.0-fold greater than that of simultaneously drawn venous plasma. Allopurinol 300 mg p.o. caused a mean 1.5-fold increase in plasma Hyp within 3 hr. In 17 patients with acute leukemia, treatment with allopurinol at 300 mg daily plus initiation of chemotherapy caused a mean 7-fold increase in plasma Hyp to 4.6 microM (range, 1 to 12 microM). The ability of Hyp to modulate the toxicity of antimetabolites affecting purine synthesis (6- diazao -5- oxonorleucine , 6-methylmercaptopurine riboside, 6-mercaptopurine, and 6-thioguanine) was determined in vitro using human B-lymphoblast (WI-L2) and promyelocytic leukemia (HL-60) cell lines. Hyp permitted growth of both cell lines in the presence of clinically achievable concentrations of all 4 drugs, but the initial culture concentrations of Hyp required were above those found in patients. Since Hyp was consumed rapidly during the culture period, the average Hyp concentrations required for the protection of cells were actually much lower. We conclude that, in patients with acute leukemia receiving allopurinol during chemotherapy, plasma Hyp concentrations are significantly elevated; the potential for antagonism of antimetabolite activity is uncertain.     

In vitro cellular immunity to Epstein-Barr virus in normal human subjects

Leukocyte migration inhibition was employed to study cell-mediated immunity (CMI) to Epstein-Barr virus (EBV) in 29 normal subjects. Anti-EBV capsid antibody titres in these subjects ranged from 0 to 1:160. Extracts of seven human lymphoblastoid cell lines carrying EBV were evaluated as the source of test antigen. Of these cell lines studied, only P₃HR-1 proved suitable as a source of EBV antigen for use in the test. Undiluted tissue-culture supernatant fluids of the EBV-carrying cell lines P₃HR-1 and SH-T₁ caused only weak or equivocal migration inhibition in normal subjects; others tested were without effect. Antigen controls consisted of extracts of the Raji cell line, which contains the EBV genome but produces no EBV antigen, and cultured human cells with no known association with EBV, all of which failed to induce migration inhibition. Cellular controls consisted of EBV sero-negative adult leukocytes and foetal cord blood leukocytes which did not respond to P₃HR-1 extract, although two of the five cord sera contained anti-EBV capsid antibody. The migration inhibition response was antigen-dose-dependent and was not affected by anti-EBV antibody capable of neutralizing the infectivity of EBV. These results show that CMI to EBV is present in normal individuals who have antibody to EBV capsid antigen.     

Immune stimulation with vitamin A therapy in patients with pulmonary neoplasms]

Based on a clinical trial, in which patients with unresectable bronchogenic cancer were treated with a combination of vitamin A plus chemotherapy, or vitamin A plus radiotherapy, a study was initiated in which vitamin A alone was given for tumor treatment. 9 male patients with metastatic unresectable squamous cell carcinoma of the lung were treated with vitamin A palmitate or 13-cis vitamin A acid. Up to seven treatment courses were given during a period of 60 weeks. Through weekly evaluation of the patients' immune status, an immune potentiating effect of the vitamin A therapy could be demonstrated. An increase of lymphocyte blastogenesis response to PHA which is significant (p less than 0.001) compared with the pretreatment values, was found in all patients at the end of one vitamin A treatment course. Increased delayed cutaneous hypersensitivity reactions were observed also in all patients. The immune potentiating effects of vitamin A therapy, as well as the demonstrated direct effect on the tumor, introduces a wide range of combination therapies.     

肺癌患者围手术期细胞免疫功能的变化

目的 探讨肺癌患者围手术期外周血T细胞亚群和NK细胞的变化及意义。方法 应用流式细胞仪检测20例肺癌患者和20例肺良性肿瘤患者手术前、术后第1天和第7天外周血T细胞亚群和NK细胞活性的变化。结果 肺癌组术前CD。3^＋、CD4^＋、CD4^＋／CD8^＋和NK细胞活性均低于肺良性肿瘤组（P〈0．01）肺癌组病人行病灶切除术后1d，CD3^＋、CD4^＋和CD4^＋／CD矿较术前降低（P〈0.01）．术后1w上述指标较术盯升高（P〈0．01），而NK细胞活性在术后ld升高（P〈0．01）．术后1w与术前相似（P〉0．05）。结论 肺癌患者的细胞免接功能低于肺良性肿瘤患者；肺癌患者术后的免疫状态呈现先降后升的变化，切除病灶能显著提高患者的免疫功能。     

Glycosylation status of haptoglobin in sera of patients with prostate cancer vs. benign prostate disease or normal subjects

We studied chemical level and glycosylation status of haptoglobin in sera of patients with prostate cancer, as compared to benign prostate disease and normal subjects, with the following results. (i) Haptoglobin level was enhanced significantly in sera of prostate cancer. (ii) Sialylated bi-antennary glycans were the dominant structures in haptoglobins from all 3 sources, regardless of different site of N-linked glycan. The N-linked glycans at N184 were exclusively bi-antennary, and showed no difference between prostate cancer vs. benign prostate disease. (iii) Tri-antennary, N-linked, fucosylated glycans, carrying at least 1 sialyl-Lewis(x/a) antenna, were predominantly located on N207 or N211 within the amino acid 203-215 sequence of the beta-chain of prostate cancer, and were minimal in benign prostate disease. Fucosylated glycans were not observed in normal subjects. A minor tri-antennary N-linked glycan was observed at N241 of the beta-chain in prostate cancer, which was absent in benign prostate disease. (iv) None of these N-linked structures showed the expected presence of disialylated antennae with GalNAcbeta4(NeuAcalpha3)Galbeta3(NeuAcalpha6)GlcNAcbetaGal, or its analogue, despite cross-reactivity of prostate cancer haptoglobin with monoclonal antibody RM2. (v) Minor levels of O-glycosylation were identified in prostate cancer haptoglobin for the first time. Mono- and disialyl core Type 1 O-linked structures were identified after reductive beta-elimination followed by methylation and mass spectrometric analysis. No evidence was found for the presence of specific RM2 or other tumor-associated glycosyl epitopes linked to this O-glycan core. In summary, levels of haptoglobin are enhanced in sera of prostate cancer patients, and the N-glycans attached to a defined peptide region of its beta-chain are characterized by enhanced branching as well as antenna fucosylation.     

Post-surgical irradiation causes cellular immune suppression in patients with breast cancer

According to several studies, even the locoregional irradiation of patients with carcinoma can cause a severe and rather alarming cellular immune defect. We thus designed a prospective research in order to study the effect of post-operative irradiation on cellular immunity in patients suffering from breast cancer. In 35 patients with breast cancer who required post-operative irradiation, four blood samples were taken at indicated point times. Nineteen out of 35 patients received post-surgical chemotherapy before irradiation. The total lymphocytes as well as CD4 and CD8 subpopulations were measured by using flow cytometry analysis. The mean T-lymphocyte (Tol) count dropped from 1487.77 to 1227.91 ( P  = 0.0013) and the CD4+ count from 674.17 to 580.91 ( P  = 0.0189). The mean value of CD8+ dropped from 421.31 to 314.00 ( P  = 0.0003). Moreover, a statistically significant difference regarding the pattern of temporal change was observed between a group of patients that received irradiation only and a group that received radiation therapy (RT) with chemotherapy ( P -values 0.0015, 0.01 and 0.092 for Tol, CD4+ and CD8+ respectively). The group of patients that received RT only presented a more rapid decrease of Tol concerning the decrease observed in the group that underwent chemotherapy and RT.     

Physical performance, depression, immune status and fatigue in patients with hematological malignancies after treatment.

BACKGROUND: Fatigue is a frequent and severe problem after treatment of patients with hematological malignancies. This symptom has been associated with anemia, reduced physical performance, mood, endocrine disorders and impaired nutritional status. Recently, it has been suggested that fatigue can be related to a persistent activation of the immune system with increased production of proinflammatory cytokines. However, there is no conclusive evidence regarding the role of the immune system in the origin of fatigue in cancer patients. PATIENTS AND METHODS: We evaluated the correlation of fatigue with thyroid function, markers of immune activity [interleukin (IL)-1alpha, IL-1 soluble receptor, IL-6, C-reactive protein and neopterin], liver and kidney function, mood and physical ability in 71 patients with hematological malignancies. All patients had been free of relapse and not received treatment (chemotherapy, radiotherapy or immune modulators) for at least 3 months. RESULTS: Fatigue was related to depression (r=0.84; P<0.0001) and reduced performance status (r=-0.61; P<0.0001). However, there was no correlation between fatigue and thyroid, liver and kidney function, anemia, albumin concentration or markers of immune activity (all r-values <0.20; P>0.05). CONCLUSIONS: We conclude that fatigue in relapse-free patients with hematological malignancies is associated with depressive mood and reduced physical performance, but not with impairment of thyroid function, anemia or persistent activation of the immune system.     

Monitoring the immune status of breast cancer patients under adjuvant chemotherapy and polychemotherapy]

The effects of various combinations of chemotherapy on the immunological status of breast cancer patients were investigated. The proportion of T cells and B cells in the peripheral blood of the patients were followed and the reactivity of lymphocytes to the mitogen phytohemagglutinin (PHA) was determined. During observation periods of 6 months it was found that patients under adjuvant chemotherapy developed only a transitory depression of B cells and T cells as well as of PHA-induced lymphocyte stimulation. However, patients under polychemotherapy showed a marked depression of these immunological markers and functions during the whole observation period. The possibility of an improved monitoring of chemotherapy in cancer patients by observation of these immunological parameters is discussed.     

Potential new applications of immunotherapy for neuroendocrine neoplasms:immune landscape,current status and future perspectives

Neuroendocrine neoplasms(NENs) are a highly heterogeneous class of tumors arising from neuroendocrine cells and peptidergic neurons. After failure of first-line treatment, patients have poor prognosis and limited treatment options. Immune checkpoint inhibitors(ICIs) may be a powerful means of increasing therapeutic efficacy for such patients, but ICIs alone have low response rates and short disease control durations in most NENs and may be effective for only a portion of the population. ICIs com...     

化疗对卵巢癌患者细胞免疫功能的影响

目的　观察化疗前后卵巢癌患者外周血T淋巴细胞亚群和NK细胞的变化 ,探讨化疗对患者的免疫损伤情况。方法　用流式细胞仪检测患者化疗前后外周血T淋巴细胞亚群和NK细胞的百分率。结果　与正常人比较 ,不论化疗前或化疗后 ,各指标均显著下降 ,有统计学意义。化疗后与化疗前比较 ,CD+ 4细胞和NK细胞明显下降 ,差异有统计学意义 ,CD+ 8细胞在前两个疗程变化不明显 ,第 3疗程下降明显 ,有统计学意义 ,后三个疗程变化虽没有统计学意义 ,但有下降趋势。CD+ 4/CD+ 8比值在第 3疗程比化疗前升高 ,其它 5个疗程均有下降 ,均有统计学意义。结论　卵巢癌患者免疫状态比正常人低 ,化疗对患者免疫功能的影响主要是对CD+ 4细胞和NK细胞的损伤 ,检测外周血T淋巴细胞亚群和NK细胞是判断患者免疫状态的重要依据