Mesothelioma environment comprises cytokines and Treg cells that suppress immune responses
Wednesday, March 15th, 2006.
European Respiratory Journal. 2006 Mar 15; [Epub ahead of print] [Link]
J.P.J.J. Hegmans 1*, A. Hemmes 1, H. Hammad 1, L. Boon 2, H.C. Hoogsteden 1, B.N. Lambrecht 1
1 Dept of Pulmonary Medicine, Erasmus MC, Rotterdam
2 Bioceros B.V., Utrecht, The Netherlands
Abstract
Malignant mesothelioma is a cancer with dismal prognosis. Our objective was to address the role of the immune system, tumour microenvironment and potential immunosuppression in mesothelioma.
Expression profiles of 80 cytokines were determined in the supernatant of mesothelioma cell lines and the original patient’s pleural effusion. Influx of immune effector cells was detected by immunohistochemistry.
Angiogenin, VEGF, TGF{beta}, ENA-78 and several other proteins involved in immune suppression, angiogenesis and plasma extravasation could be detected in both supernatant and pleural effusion. Surrounding stroma and/or infiltrating cells were the most likely source of HGF, MIP-1{delta}, MIP-3{alpha}, NAP-2, and PARC that can cause leukocyte infiltration and activation. There was a massive influx of CD4+ and CD8+ T lymphocytes and macrophages, but not of dendritic cells, in human mesothelioma biopsies. We further demonstrated that human mesothelioma tissue contained significant amounts of Foxp3+CD4+CD25+ regulatory T cells. When these CD25+ regulatory T cells were depleted in an in vivo mouse model, survival was increased.
Mesothelioma is infiltrated by immune effector cells, but also contains cytokines and regulatory T cells that suppress an efficient immune response. Immunotherapy of mesothelioma might be more effective when combined with drugs that eliminate or control regulatory T cells.
Glossary
- prognosis
- (prog-no-sis) a prediction of the course of disease; the outlook for the cure of the patient. For example, women with breast cancer that was detected early and who received prompt treatment have a good prognosis.
- lymphocytes
- a type of white blood cell that helps the body fight infection.
- immunotherapy
- (im-mune-no-THER-uh-pee) treatments that promote or support the body's immune system response to a disease such as cancer.
- immunosuppression
- (im-mune-no-suh-PREH-shun) a state in which the body's immune system does not respond as it should. This condition may be present at birth, or it may be caused by certain infections (such as human immunodeficiency virus or HIV), or by certain cancer therapies, such as cancer-cell killing (cytotoxic) drugs, radiation, and bone marrow transplantation.
- immune system
- the complex system by which the body resists infection by microbes such as bacteria or viruses and rejects transplanted tissues or organs. The immune system may also help the body fight some cancers.
- cell
- the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.
- cancer
- malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.
- angiogenesis
- (an-gee-o-JEN-uh-sis) the formation of new blood vessels. Some cancer treatments work by blocking angiogenesis, thus preventing blood from reaching the tumor.
- tissue
- a collection of cells, united to perform a particular function.
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
- pleural effusion
- an abnormal accumulation of fluid, usually caused by trauma or disease, in the pleural space.
