title: Regulatory T cells and cytokines in malignant pleural effusions secondary to mesothelioma and carcinoma.
abstract: Immunotherapy against a variety of malignancies, including pleural-based malignancies, has shown promise in animal models and early human clinical trials, but successful efforts will need to address immunosuppressive factors of the tumor and host, particularly certain cytokines and CD4(+) CD25(+) regulatory T cells (Treg). Here, we evaluated the cellular and cytokine components of malignant pleural effusions from 44 patients with previously diagnosed mesothelioma, non-small cell lung cancer (NSCLC), or breast cancer and found significant differences in the immune profile of pleural effusions secondary to mesothelioma vs. carcinoma. Although a high prevalence of functionally suppressive CD4(+) CD25(+) T cells was found in carcinomatous pleural effusions, mesothelioma pleural effusions contained significantly fewer CD4(+) CD25(+) T cells. Activated CD8(+) T cells in pleural fluid were significantly more prevalent in mesothelioma than carcinoma. However, there is clear patient-to-patient variability and occasional mesothelioma patients with high percentages of CD4(+) CD25(+) pleural effusion T cells and low percentages of CD8(+) CD25(+) pleural effusion T cells can be identified. Mesothelioma pleural effusions contained the highest concentrations of the immunosuppressive cytokine transforming growth factor (TGF)-beta. Thus, the contribution of cellular and cytokine components of immunosuppression associated with malignant pleural effusions varies by tumor histology and by the individual patient. These results have implications for the development of immunotherapy directed to the malignant pleural space, and suggest the need to tailor immunotherapy to overcome immunosuppressive mechanisms in tumor environments.
authors.affiliation: Thoracic Oncology Research Laboratory, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: DeLong
authors.forename: Richard G
authors.initials: RG
authors.lastname: Carroll
authors.forename: Adam C
authors.initials: AC
authors.lastname: Henry
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Sajjad
authors.initials: S
authors.lastname: Ahmad
authors.forename: Michael S
authors.initials: MS
authors.lastname: Leibowitz
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Sterman
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.forename: Steven M
authors.initials: SM
authors.lastname: Albelda
authors.forename: Robert H
authors.initials: RH
authors.lastname: Vonderheide
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D015704:CD4 Antigens / Q000032:analysis; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology; D008654:Mesothelioma / Q000276:immunology* / Q000473:pathology; D016066:Pleural Effusion, Malignant / Q000276:immunology* / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D015375:Receptors, Interleukin-2