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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bui, Jack D. Crocker, Paul R. Varki, Nissi M. Secrest, Patrick Verhagen, Andrea Zhang, Jiquan Varki, Ajit Pearce, Oliver M. T. Läubli, Heinz |
| Description | Author Affiliation: Pearce OM ( Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Department of Pathology, University of California, San Diego, La Jolla, CA 92093.); |
| Abstract | Compelling evidence for naturally occurring immunosurveillance against malignancies informs and justifies some current approaches toward cancer immunotherapy. However, some types of immune reactions have also been shown to facilitate tumor progression. For example, our previous studies showed that although experimental tumor growth is enhanced by low levels of circulating antibodies directed against the nonhuman sialic acid N-glycolyl-neuraminic acid (Neu5Gc), which accumulates in human tumors, growth could be inhibited by anti-Neu5Gc antibodies from a different source, in a different model. However, it remains generally unclear whether the immune responses that mediate cancer immunosurveillance vs. those responsible for inflammatory facilitation are qualitatively and/or quantitatively distinct. Here, we address this question using multiple murine tumor growth models in which polyclonal antibodies against tumor antigens, such as Neu5Gc, can alter tumor progression. We found that although growth was stimulated at low antibody doses, it was inhibited by high doses, over a linear and remarkably narrow range, defining an immune response curve (IRC; i.e., inverse hormesis). Moreover, modulation of immune responses against the tumor by altering antibody avidity or by enhancing innate immunity shifted the IRC in the appropriate direction. Thus, the dualistic role of immunosurveillance vs. inflammation in modulating tumor progression can be quantitatively distinguished in multiple model systems, and can occur over a remarkably narrow range. Similar findings were made in a human tumor xenograft model using a narrow range of doses of a monoclonal antibody currently in clinical use. These findings may have implications for the etiology, prevention, and treatment of cancer. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 16 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antibodies, Neoplasm Immunology Hormesis Neoplasms Pathology Adaptive Immunity Animals Antibodies, Monoclonal Antibody Affinity Burkitt Lymphoma Cell Line, Tumor Cell Proliferation Disease Models, Animal Disease Progression Immunoglobulin G Inflammation Killer Cells, Natural Macrophages Mice Mice, Inbred C57BL Mice, Nude Neuraminic Acids Sialic Acid Binding Immunoglobulin-like Lectins Metabolism Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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