Adenocarcinoma ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery ; Adult ; Antigens, Neoplasm ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery ; Chemoradiotherapy, Adjuvant ; Chemotherapy, Adjuvant ; Female ; Humans ; Hysterectomy ; Iridium Radioisotopes ; therapeutic use ; Middle Aged ; Neoadjuvant Therapy ; methods ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Preoperative Period ; Radiotherapy, Adjuvant ; Retrospective Studies ; Serpins ; metabolism ; Treatment Outcome ; Uterine Cervical Neoplasms ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery

OBJECTIVETo analyze the expression of co-stimulatory molecules PD-1/PD-L1 in peripheral blood mononuclear cells in lung cancer patients, and to explore its biological significance.

METHODSOne hundred and thirty-three lung cancer patients, 25 lung infection patients and 23 healthy donors were enrolled in this study. 100 µl of whole blood from these subjects were collected. Multi-color immunofluorescence staining and flow cytometry were used to detect PD-1/PD-L1 expression. The results were statistically analyzed.

RESULTSThe expression level of CD3⁺CD8⁺ T cells in the lung cancer patients was (38.83 ± 1.74)%, significantly lower than that in the control group [(43.25 ± 3.35)%, P < 0.05]. CD8⁺CD28⁺ T cell subset in the peripheral blood of lung cancer patients was (17.73 ± 1.21)% significantly lower than that of the healthy donors [(27.96 ± 2.72)%, P < 0.01]. The CD8⁺CD28⁻ T cell subset was (21.19 ± 1.92)% in the lung cancer patients, significantly higher than that of the healthy control group [(15.18 ± 2.93)%, P < 0.05]. The expression level of PD-1 on the surface of CD8⁺CD28⁺ T cells was (10.67 ± 1.12)% in the group of lung cancer patients, significantly higher than that of the control group [(5.32 ± 1.58)%, P < 0.01]. It was also found that the expression of PD-1 on CD8⁺CD28⁻ T cells was up-regulated in the group of lung cancer patients (7.46 ± 1.25)%, significantly higher than that of the healthy control group [(2.68+1.07)%, P < 0.01]. The expression level of PD-L1 on CD68⁺ cells in the lung cancer patients was (16.03 ± 2.06)%, significantly higher than that of the healthy control group [(9.32 ± 2.00)%, P < 0.05].

CONCLUSIONUp-regulation of PD-1/PD-L1 on peripheral blood cells in lung cancer patients negatively regulates the lymphocytes, inhibits the immune response for killing tumor cells, and promotes tumor development and immune escape.

Adenocarcinoma ; blood ; pathology ; B7-H1 Antigen ; metabolism ; CD28 Antigens ; metabolism ; CD3 Complex ; metabolism ; CD8 Antigens ; metabolism ; Carcinoma, Large Cell ; blood ; pathology ; Carcinoma, Squamous Cell ; blood ; pathology ; Case-Control Studies ; Female ; Humans ; Lung Neoplasms ; blood ; pathology ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor ; metabolism ; Small Cell Lung Carcinoma ; blood ; pathology ; T-Lymphocytes ; immunology ; metabolism ; Up-Regulation

OBJECTIVETo explore the clinical significance of cytokeratin 19 fragments test in the diagnosis of nasopharyngeal carcinoma.

METHODSThe study included 102 cases of nasopharyngeal carcinoma, 90 cases of nasal polyp/nasopharyngitis, and 150 healthy individuals. RT-PCR was used to detect CK19 mRNA expression and Western blot to detect CK19 fragment protein expression in tissues of nasopharyngeal carcinoma. Expression of CK19-2G2 was examined by immunohistochemistry. Chemiluminescence analysis was used to detect the serum levels of CK19-2G2, and ELISA to detect that of EB-VCA IgA.

RESULTSAmong 102 cases of nasophryngeal carcinoma, 64 showed CK19 mRNA expression by RT-PCR, 60 showed CK19 protein fragments in tumor tissues by Western blot, and 66 showed expression of CK19-2G2 by immunohistochemistry in nasopharyngeal carcinoma, including strong positivity in 20 cases, moderate in 34 cases and weak in 12 cases. The sensitivity and specificity of CK19-2G2 in the diagnosis of nasopharyngeal carcinoma were 49.0% and 89.2%, and those of EB-VCA IgA were 52.9% and 85.4%, respectively. The combined detection of CK19-2G2 and EB-VCA IgA increased the sensitivity to 73.5% while the specificity remained at 80.0%.

CONCLUSIONSHigh levels of CK19-2G2 fragment expressed in tissue and serum are present in patients with nasopharyngeal carcinoma. The serum level of CK19-2G2 is helpful in the diagnosis of nasopharyngeal carcinoma. Furthermore, the combination of serum CK19-2G2 and EB-VCA IgA improves the detection sensitivity.

Adult ; Aged ; Antigens, Viral ; blood ; Blotting, Western ; Capsid Proteins ; blood ; Carcinoma, Squamous Cell ; diagnosis ; metabolism ; pathology ; Herpesvirus 4, Human ; immunology ; Humans ; Immunoglobulin A ; blood ; Immunohistochemistry ; Keratin-19 ; blood ; metabolism ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnosis ; metabolism ; pathology ; Neoplasm Staging ; Peptide Fragments ; blood ; metabolism ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity

Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; metabolism ; Antigens, Neoplasm ; immunology ; metabolism ; Biomarkers, Tumor ; metabolism ; Carcinoma, Squamous Cell ; diagnosis ; metabolism ; pathology ; Cell Cycle Proteins ; immunology ; metabolism ; Cervical Intraepithelial Neoplasia ; diagnosis ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; DNA Topoisomerases, Type II ; immunology ; metabolism ; DNA-Binding Proteins ; immunology ; metabolism ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Middle Aged ; Minichromosome Maintenance Complex Component 2 ; Nuclear Proteins ; immunology ; metabolism ; Uterine Cervical Neoplasms ; diagnosis ; metabolism ; pathology ; Young Adult

Tumor-associated macrophages (TAMs) can elicit contrasting effects on tumor progression, depending on different tumor microenvironment. This study aimed to explore the correlation between TAM infiltration and clinicopathologic characteristics, metastasis, and prognosis of supraglottic laryngeal carcinoma. TAMs in intratumoral and peritumoral regions of 84 specimens of supraglottic laryngeal carcinoma tissues were detected by immunohistochemical staining with monoclonal CD68 antibody. The density of peritumoral CD68(+) TAMs in recurrence cases (9/11) and in dead cases (17/23) were significantly higher than those in non-recurrence cases (33/73) and in survival cases (25/61), with significant differences (P = 0.024 and 0.007, respectively). The Kaplan-Meier survival analysis showed a significant relationship between the infiltration of both intratumoral and peritumoral CD68(+) TAMs and the overall survival of patients. The 5-year survival rate was significantly lower in the group with a high density of intratumoral CD68(+) TAMs than in the group with a low density (39.6% vs. 82.5%, P < 0.05). Similarly, the 5-year survival rate was significantly lower in the group with a high density of peritumoral CD68(+) TAMs than in the group with a low density (50.6% vs. 73.1%, P < 0.05). Cox regression analysis revealed that T classification, distant metastasis, and intratumoral or peritumoral CD68(+) TAMs were independent factors for disease-free survival, whereas T classification and intratumoral CD68(+) TAMs were independent factors for overall survival. The results indicate that TAM infiltration in supraglottic laryngeal carcinoma can be used to predict metastasis and prognosis and is an independent factor for prognosis.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Carcinoma, Squamous Cell ; immunology ; pathology ; Disease-Free Survival ; Female ; Humans ; Laryngeal Neoplasms ; immunology ; pathology ; Lymphatic Metastasis ; Macrophages ; immunology ; pathology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Survival Rate

OBJECTIVETo investigate the efficacy and toxicity of neoadjuvant chemotherapy with paclitaxel and carboplatin or cisplatin for patients with locally advanced cervical cancer.

METHODSA total of 70 patients with locally advanced cervical cancer were treated with neoadjuvant chemotherapy with paclitaxel and carboplatin or cisplatin in our department from July 2007 to May 2010. The stage distribution among the patients included 45 stage IB2, 21 stage IIa, and 4 stage IIb. Of the 70 patients, 6 were G1, 26 were G2, 32 were G3, and the rest 6 patients were not histologically classified. Sixty-five patients had squamous cell carcinoma, 3 had adenocarcinoma, and 2 patients had adenosquamous cell carcinoma. The clinicopathological parameters were analyzed, and their impact on tumor response were investigated.

RESULTSOf the 70 patients, 14 (20.0%) showed a complete response, 37 (52.9%) had a partial response to chemotherapy, making an overall response rate of 72.9%. Sixty-eight (95.7%) patients underwent surgery, and among them 12 (17.1%) pathological CR were identified. Eleven (16.2%) patients were found to have lymph node metastasis after surgery. Response rates of stage Ib2 and IIa patients were 73.7% and 52.3%, respectively, P<0.05. Patients with SCC exhibited a better response rate than patients with adenocarcinoma and adenosquamous cell carcinoma (73.8% vs. 60.0%). Initial tumor volume, histological classification and cycles of neoadjuvant chemotherapy were not significantly correlated with the response rate.

CONCLUSIONPaclitaxel and carboplatin or cisplatin regimen is a promising therapy with definite short-term efficacy, can improve the resection rate with tolerable side effects, and is an applicable option of treatment for patients with locally advanced cervical cancer in the neoadjuvant setting.

Adenocarcinoma ; drug therapy ; immunology ; pathology ; surgery ; Adult ; Antigens, Neoplasm ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Adenosquamous ; drug therapy ; immunology ; pathology ; surgery ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; pathology ; surgery ; Chemotherapy, Adjuvant ; Cisplatin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; methods ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Remission Induction ; Serpins ; metabolism ; Uterine Cervical Neoplasms ; drug therapy ; immunology ; pathology ; surgery

Aged, 80 and over ; Antibodies, Monoclonal ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Diagnosis, Differential ; Granuloma ; metabolism ; pathology ; Humans ; Keratins ; immunology ; Male ; Mucin-1 ; metabolism ; Skin Neoplasms ; metabolism ; pathology

BACKGROUND AND OBJECTIVECytokine-induced killer (CIK) cells and autologous dendritic cells-CIK (DC-CIK) cells co-cultured with autologous dendritic cells (DCs) and CIK cells are commonly used for immunotherapy recently. We compared the anti-tumor immune response of CIK cells, autologous DC-CIK cells, and semi-allogeneic DC-CIK cells to explore a more effective anti-tumor adoptive immunotherapy approach.

METHODSPeripheral monocytes were isolated from patients with renal carcinoma, lung cancer, or maxillary squamous cell carcinoma and their healthy adult children. Isolated cells were cultured and induced as DCs and CIK cells in vitro. CIK cells from patients were co-cultured with autologous DCs and DCs from their children respectively, generating DC-CIK cells and semi-allogeneic DC-CIK cells. The anti-tumor activities of autologous CIK cells, autologous DC-CIK cells, and semi-allogeneic DC-CIK cells were measured by LDH assay. Intracellular staining was used to test the secretion of cytokines. Flow cytometry was applied for detecting the phonotype changes of these three types of cells. Cell proliferation and cell apoptosis were detected by 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) and Annexin V/PI respectively.

RESULTSCompared with autologous CIK cells and DC-CIK cells, semi-allogeneic DC-CIK cells significantly enhanced the anti-tumor activity and IFN-gamma secretion, reduced IL-4 secretion, increased the ratio of CD3(+)CD56(+) cells and CD3(+)CD8(+) cells, decreased the number of CD4(+)CD25(+) cells, promoted cell proliferation, and lessened cell apoptosis.

CONCLUSIONSSemi-allogeneic DC-CIK cells had a stronger anti-tumor effect than did autologous CIK cells and DC-CIK cells. Our results provided experimental evidence for clinical application of DC-CIK cells.

Apoptosis ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; Cytokine-Induced Killer Cells ; cytology ; immunology ; metabolism ; Cytokines ; metabolism ; Cytotoxicity, Immunologic ; Dendritic Cells ; cytology ; immunology ; metabolism ; Hep G2 Cells ; Humans ; Immunotherapy, Adoptive ; Interferon-gamma ; secretion ; Interleukin-4 ; secretion ; K562 Cells ; Kidney Neoplasms ; metabolism ; pathology ; L-Lactate Dehydrogenase ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; Maxillary Neoplasms ; metabolism ; pathology

OBJECTIVETo study the clinicopathologic characteristics of thymic epithelial tumors and to evaluate the diagnostic reproducibility and clinical relevance of the 2004 WHO histologic classification system.

METHODSThe morphology and immunophenotype of 52 cases of thymic epithelial tumor were reviewed. The tumors were classified according to the new WHO classification system and the clinical data were analyzed.

RESULTSOf the 52 cases studied, 45 were thymomas and 7 were thymic carcinomas. Amongst the 45 cases of thymoma, 6 (13.4%) were type A, 15 (33.3%) were type AB, 4 (8.9%) were type B1, 9 (20.0%) were type B2, 9 (20.0%) were type B3 and 2 (4.4%) were metaplastic thymoma. Amongst the 7 cases of thymic carcinoma, 6 were squamous cell carcinomas and 1 was neuroendocrine carcinoma. The commonest presentations were cough and chest pain. Some cases were incidentally discovered by routine physical examination. Thirteen cases (25.0%) of thymoma were associated with myasthenia gravis. CT scan showed that 49 cases (94.2%) were located in the anterior mediastinum. All cases of type A, AB and B1 thymoma and most cases of B2 thymoma appeared as well-defined homogeneous mass, whereas a few cases of type B2 thymoma and most cases of type B3 thymoma and thymic carcinoma were poorly demarcated and heterogeneous. According to Masaoka staging system, 20 cases (41.7%) belonged to stage I, 15 cases (31.3%) stage II, 11 cases (22.9%) stage III and 2 cases (4.1%) stage IV. The histologic subtypes of thymic epithelial tumors significantly correlated with the clinical stages (chi(2) = 32.5, P < 0.01).

CONCLUSIONSThe 2004 revision of WHO histologic classification system for thymic epithelial tumors shows a high degree of reproducibility. Correlation with the radiologic, clinical and prognostic parameters is helpful in determining the management strategy for individual patients.

Adult ; Aged ; Antibodies, Monoclonal ; analysis ; Antigens, CD20 ; metabolism ; CD5 Antigens ; metabolism ; Carcinoma, Neuroendocrine ; classification ; diagnostic imaging ; metabolism ; pathology ; Carcinoma, Squamous Cell ; classification ; diagnostic imaging ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Keratins ; immunology ; Male ; Middle Aged ; Myasthenia Gravis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Radiotherapy, Adjuvant ; Retrospective Studies ; Thymoma ; classification ; diagnostic imaging ; metabolism ; pathology ; Thymus Neoplasms ; classification ; diagnostic imaging ; metabolism ; pathology ; Tomography, X-Ray Computed

PURPOSE: Forkhead box p3 (Foxp3) positive T regulatory cells (Tregs) have a functionally immunosuppressive property that prevents effector cells from acting against self in autoimmune diseases or a tumor. It is known that Tregs may be highly relevant in cancer progression. Dendritic cells (DCs) induce cutaneous immune response, however several studies have suggested that DCs are involved in immunosuppression. The aim of this study is to evaluate the prevalence of Tregs and DCs infiltration in cutaneous premalignant and malignant squamous lesions. MATERIALS AND METHODS: We evaluated Tregs and DCs in skin tissue samples obtained from 83 patients with actinic keratosis, Bowen's disease or squamous cell carcinoma by immunohistochemistry. RESULTS: The prevalence of Tregs and DCs was significantly higher in squamous cell carcinoma and Bowen's disease than in actinic keratosis. In addition, the number of DCs was closely correlated with the prevalence of Tregs, and DCs were also located in direct proximity to Tregs. CONCLUSION: Tregs is related to cutaneous squamous tumor progression.
Bowen's Disease/immunology/metabolism/pathology ; Carcinoma, Squamous Cell/immunology/metabolism/pathology ; Dendritic Cells/immunology/metabolism/pathology ; Forkhead Transcription Factors/immunology/*metabolism ; Humans ; Immune Tolerance ; Keratosis, Actinic/immunology/metabolism/pathology ; Skin Neoplasms/*immunology/metabolism/pathology ; T-Lymphocytes, Regulatory/*immunology/metabolism/pathology