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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphocytopenia is a prognostic factor for shorter survival in advanced lung cancer and it is likely related to an interleukin-2 (IL-2) deficiency occurring during cancer progression. Major surgery itself for cancer is known to induce lymphocytopenia in the postoperative period. Postoperative lymphocyte decrease in colorectal cancer can be prevented by preoperative administration of recombinant human (rhIL-2), indicating that it is possible to drive appropriately important host defence agents during critical events, such as major surgery. The aim of this study is to verify if recombinant human interleukin-2 (rhIL-2) administered preoperatively is able to prevent the lymphocyte decrease occurring after radical surgery in operable lung cancer. This phase II study included 40 patients with operable NSCLC screened as stage II or IIIA, randomized to receive rhIL-2, 9000000 IU subcutaneously twice daily for 3 days before surgery (treated group, 20 patients) or not (control group, 20 patients). At baseline, there were no significant differences in total lymphocyte number and lymphocyte subsets (T-cell, T-helper, CD8+, natural killer, CD4/CD8 ratio) between groups. Postoperatively the control group showed a decrease in total lymphocyte count, T-lymphocyte count, T-helper cell number and CD4/CD8 ratio, significant at the 14th postoperative day relative to baseline values. In contrast, in the rhIL-2 treated group, at the 3rd and at the 14th postoperative days, a significant increase was observed over both baseline and control group values of total lymphocyte count, T-cells and T-helper cells. NK cell number increased significantly only over the control group. CD4/CD8 ratio was increased at the 14th postoperative day significantly over both baseline and control values. At pathological staging after surgery, four patients in the rhIL-2 group and four in the control group resulted in stage pIIIB; one patient in the rhIL-2 group resulted in stage IV (contralateral metastasis). Indeed, 15/20 rhIL-2 treated patients and 16/20 control patients were radically operated. After a 24-month follow-up, 12/20 rhIL-2 treated patients were alive and 8/15 radically operated were disease-free; 8/20 control patients were alive and 4/16 radically operated were disease-free. Toxicity was mild to moderate and easy manageable; treatment was suspended in one patient due to skin rash with hypotension grade II. The preoperative administration of rhIL-2 is feasible and prevents lymphocyte decrease occurring postoperatively after surgery for lung cancer. Further studies are required to assess the impact on survival.
Lung Cancer 1998 Jun
PMID:Phase-II randomized study of pre-operative IL-2 administration in operable NSCLC. 973 54

High levels of soluble lymphocyte antigens have been described in a large number of tumors and, particularly, in hematopoietic neoplasms. As previously reported, many antitumor immune responses are IL-2 dependent: clinical observations indicate that a worse survival in advanced tumor patients is related with a decrease of soluble IL-2 levels. A soluble form of CD8 has been described: as found in Hodgkin's disease and acute lymphoblastic leukemia, sCD8 levels have a prognostic value. To explain the significance of these soluble molecules in solid tumors, we a) determinated sIL-2R and sCD8 in 84 patients; b) correlated the expression of p55 chain of IL-2R and CD8 antigen on the cell-surface of peripheral lymphocytes to sIL-2R and sCD8 levels; c) analyzed endogenous IL-2R levels in patients with lung cancer. An increase of sIL-2R was found in 82% of cases, while high levels of sCD8 were observed in 32%; no correlation was observed between sIL-2R and the expression of p55 on the surface of peripheral lymphocytes: IL-2 levels in patients with NSCLC were significatively reduced, when compared to healthy controls, with an inverse relationship between endogenous IL-2 concentration and sIL-2R levels. Whatever may be the physiopathological mechanism of the increase of sIL-2 observed in solid tumors, this rise may contribute to the immunodepression correlated to neoplastic disease. Therefore, higher levels of sIL-2R/IL-2 ratio has a negative biologic prognostic significance. We think that determinating CD8 antigen in the serum can offer a more sensitive and specific measurement of activation of suppressor/cytotoxic T-lymphocytes.
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PMID:Soluble interleukin-2 receptor and soluble CD8 antigen levels in serum from patients with solid tumors. 985 47

The purpose of this work was to evaluate the normal lymphocyte phenotype in the bronchoalveolar lavage fluid (BALF). BAL was carried out in 12 untreated healthy nonsmoking volunteers and in 9 cigarette smokers. For the analysis of lymphocyte subsets by two-color flow cytometry, the monoclonal antibodies used were directed anti: CD3, CD4, CD8, CD16, CD19, D25, CD45, CD56 and anti HLA-DR. An increase in the total number of cells in BALF of smoking persons and increased proportion of macrophages was observed. The percentage of CD8+ lymphocytes was 1.7 times higher, whereas the proportions of CD4+ cells, and a CD4+/CD8+ ratio were lower 1.5 and 2.6 times, respectively, in the BALF of cigarette smoking persons when compared with nonsmoking volunteers. The changes did not depend on the age of the person. In conclusion, we suggest that the decreased CD4/CD8 ratio and the elevated CD8 T cell subset may be regarded as a potential risk factor associated with clinically asymptomatic lung cancer. Moreover, in the interpretation of BALF from patients with pulmonary diseases cell proportions of nonsmoking and of smoking persons should be compared with the respective controls.
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PMID:Flow cytometric evaluation of lymphocyte subpopulations in BALF of healthy smokers and nonsmokers. 1009 47

The prognostic significance of immune cell infiltrates in surgically resected human lung cancer was investigated in 710 patients. Lymphoid infiltrates were quantified on both standard H&E stained sections and, in a subset of 95 cases, using immunohistochemistry and antibodies to CD3, CD8, CD57, CD68, CD79a and S100 to identify various immune cell types. Subjective grading (low, moderate, high) of lymphoid cell infiltrates on H&E sections of tumour and measurement, using image analysis, of overall level of tumour infiltration by any of the immunohistochemically labelled specific immune cell types of the stained sections showed no prognostic significance. However, when a distinction between peritumoural and intratumoural infiltration by particular cell types was made, intratumoural infiltration by high levels of CD3+ and S100+ cells was associated with longer post-operative survival (P = 0.02 and P = 0.045, respectively). In lung cancer, subjective assessment of tumour lymphoid infiltration and overall levels of infiltration by particular immune cell types carries no prognostic significance. Intratumoural infiltration by relatively high numbers of CD3+ T-lymphocytes and Langerhans cells (S100+) is associated with a better patient outcome.
Lung Cancer 2000 Jan
PMID:Immune cell infiltrates and prognosis in primary carcinoma of the lung. 1067 81

Several immunologic parameters have been reported to correlate with the clinicopathologic status of lung cancer patients. However, these studies were based on relatively small numbers of patients and often yielded conflicting results. We prospectively studied cellular immunologic parameters related to age, gender, and stage in lung cancer patients. We obtained pretreatment peripheral blood samples from 287 lung cancer patients. Lymphocyte subsets (percentage of lymphocytes positive for CD3, CD4, CD8, HLA-DR, or representing FcgammaR IIIa-positive T cells), natural killer (NK) cell activity, and lymphoblastogenesis (LB) after stimulation by phytohemagglutinin (PHA) were evaluated. Significant decline was seen in older patients in percentages of cells positive for CD3 or CD4, in the CD4/CD8 ratio and in LB. The percentage of FcgR IIIa-positive T cells increased with age. LB as well as CD4 positivity were significantly greater in women than in men. NK cell activity showed the greatest cytotoxic responses in stage IIIA, with significantly less response in stage IV than in IIIA. Node-negative patients showed higher reactivities for LB and lower positivity for HLA-DR than node-positive patients. Patients with no distant metastases had a higher level of NK cell activity than patients with distant metastases. Immune parameters are variously related to age, gender, and the stage in lung cancer patients, some may prove to be useful predictors of survival.
Lung Cancer 2000 May
PMID:Cellular immunologic parameters related to age, gender, and stage in lung cancer patients. 1071 31

The antitumor efficiency of secondary lymphoid organ chemokine (SLC), a CC chemokine that chemoattracts both dendritic cells (DCs) and T lymphocytes,was evaluated in SV40 large T-antigen transgenic mice that develop bilateral multifocal pulmonary adenocarcinomas. Injection of recombinant SLC in the axillary lymph node region led to a marked reduction in tumor burden with extensive lymphocytic and DC infiltration of the tumors and enhanced survival. SLC injection led to significant increases in CD4 and CD8 lymphocytes as well as DC at the tumor sites, lymph nodes, and spleen. The cellular infiltrates were accompanied by the enhanced elaboration of Type 1 cytokines and the antiangiogenic chemokines IFN-gamma inducible protein 10, and monokine induced by IFN-gamma (MIG). In contrast, lymph node and tumor site production of the immunosuppressive cytokine transforming growth factor beta was decreased in response to SLC treatment. In vitro, after stimulation with irradiated autologous tumor, splenocytes from SLC-treated mice secreted significantly more IFN-gamma and granulocyte macrophage colony-stimulating factor, but reduced levels of interleukin 10. Significant reduction in tumor burden in a model in which tumors develop in an organ-specific manner provides a strong rationale for additional evaluation of SLC in regulation of tumor immunity and its use in lung cancer immunotherapy.
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PMID:Secondary lymphoid organ chemokine reduces pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma. 1152 34

The changes in local immunology play an important role in lung cancer development. We used bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) for the analysis of cell profiles in patients with primary lung cancer. Twenty-one patients with confirmed primary lung cancer and 13 healthy volunteers were investigated. All persons were smokers. The analysis of T-cell subsets was performed with a flow cytometry method and with the following antibodies: anti CD3, CD4, CD8, CD16, CD25, CD45, CD56, and HLA-DR. We found differences in the proportion of lymphocytes between BALF and PB, and a higher proportion of T cells and a lower proportion of B and natural-killer (NK) cells in BALF. There was a significant difference in the proportion of T-cytotoxic/suppressor lymphocytes, which was elevated in the BALF of patients and decreased in patients' PB. The T-helper:T-cytotoxic/suppressor (Th:Tc/s) ratio was significantly lower in the BALF of patients. These changes were visible in patients with a small cell type. The percentage of T cells with the alpha chain of receptor to IL-2 (IL -R) was lower in the BALF of patients than in the control group. Our observations reflect local changes in lung environment in patients affected with lung cancer.
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PMID:T-cell subtypes in bronchoalveolar lavage fluid and in peripheral blood from patients with primary lung cancer. 1159 2

A DNA vaccine encoding human carcinoembryonic antigen (CEA) broke peripheral T-cell tolerance toward this tumor self-antigen expressed by Lewis lung carcinoma stably transduced with CEA in C57BL/6J mice transgenic for CEA. This vaccine, delivered by oral gavage with an attenuated strain of Salmonella typhimurium (SL7207), and boosted with an antibody-IL2 fusion protein, induced tumor-protective immunity mediated by MHC class I antigen-restricted CD8(+) T cells, resulting in eradication of subcutaneous tumors in 100% of mice and prevention of experimental pulmonary metastases in 75% of experimental animals. Both CTL and antigen-presenting dendritic cells were activated as indicated by a decisive increase in their respective activation markers CD2, CD25, CD28 as well as CD48 and CD80. The antitumor effects of this CEA-based DNA vaccine obtained in prophylactic settings, suggest that this approach could lead to the rational design of effective treatment modalities for human lung cancer.
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PMID:An oral DNA vaccine against human carcinoembryonic antigen (CEA) prevents growth and dissemination of Lewis lung carcinoma in CEA transgenic mice. 1167 5

The expression of surface markers of blood lymphocytes was studied in 32 lung cancer patients. Tumor process involved enhanced expression of the activation markers CD25, CD71 and HLA-DR as well as differentiation antigens CD4, CD8, CD22 and CD16. The expression of the markers was higher than in control, irrespective of stage, localization and histological pattern of tumor. It is suggested that increased expression of surface markers should be accounted for by tumor-induced suppression of the immune system in lung cancer.
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PMID:[Phenotype of peripheral blood lymphocytes in patients with lung cancer]. 1171 Feb 85

Immunologic prognostic factors in lung cancer have not been fully clarified. We report the results of a prospective study undertaken to clarify the correlation between various cellular immunologic parameters and the survival of lung cancer patients. A total of 287 lung cancer patients were enrolled in this study. Representative in vitro cellular immune activities including lymphoblastogenesis and natural killer cell activities, in addition to the percentage of main lymphocyte subsets (CD3, CD4, CD8, HLA-DR, and Fc gamma R III on T cells) in the peripheral blood were evaluated before the initiation of therapy. The immune factors that influence the prognosis were analyzed by the log rank test and a multivariate analysis using the Cox proportional hazards model. Univariate analysis of the survival curves revealed a significant difference with regard to disease stage (P<0.0001), age (P=0.007), gender (P=0.0037), and HLA-DR (%) (P=0.048), when all the non-small cell lung cancer (NSCLC) patients (n=257) were analyzed together. This analysis, based on the histologic type, revealed that HLA-DR (%) was a significant predictor of survival in squamous cell carcinoma (P=0.0013) and small cell carcinoma (P=0.0025). A decreased CD4/CD8 ratio in small cell carcinoma (P=0.0062) and male gender in adenocarcinoma (P=0.0086) were factors associated with a worse prognosis. Multivariate analysis identified a significant correlation between survival and disease stage (P<0.0001) and gender (P=0.0243) in adenocarcinoma, disease stage (P<0.0001), age (P=0.0436) and HLA-DR (%) (P=0.0142) in squamous cell carcinoma, and HLA-DR (%) (P=0.0212) and CD4/CD8 (P=0.0112) in small cell carcinoma, suggesting independent prognostic significance. A variety of immunologic indices have prognostic significance for the different types of lung cancer. Among these, the HLA-DR (%) in the peripheral blood is the most reliable factor for squamous cell carcinoma and small cell carcinoma.
Lung Cancer 2002 Aug
PMID:Immunologic parameters as significant prognostic factors in lung cancer. 1214 Jan 39


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