| Natural killer (NK): dendritic cell (DC) cross talk induced by therapeutic monoclonal antibody triggers tumor antigen-specific T cell immunity. | |
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MedLine Citation:
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PMID: 21717064 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tumor antigen (TA)-targeted monoclonal antibodies (mAb), trastuzumab, cetuximab, panitumumab, and rituximab, have been among the most successful new therapies in the present generation. Clinical activity is observed as a single agent, or in combination with radiotherapy or chemotherapy, against metastatic colorectal cancer, head and neck cancer, breast cancer, and follicular lymphoma. However, the activity is seen only in a minority of patients. Thus, an intense need exists to define the mechanism of action of these immunoactive mAb. Here, we discuss some of the likely immunological events that occur in treated patients: antibody-dependent cellular cytotoxicity (ADCC), cross talk among immune cells including NK cells and dendritic cells (DCs), and generation of TA-specific T lymphocyte responses. We present evidence supporting the induction of "NK:DC cross talk," leading to priming of TA-specific cellular immunity. These observations show that mAb-mediated NK cell activation can be greatly enhanced by the action of stimulatory cytokines and surface molecules on maturing DC and that NK:DC interaction facilitates the recruitment of both NK cells and DC to the tumor site(s). The cooperative, reciprocal stimulatory activity of both NK cells and DC can modulate both the innate immune response in the local tumor microenvironment and the adaptive immune response in secondary lymphoid organs. These events likely contribute to clinical activity, as well as provide a potential biomarker of response to mAb therapy. |
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Authors:
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Steve C Lee; Raghvendra M Srivastava; Andrés López-Albaitero; Soldano Ferrone; Robert L Ferris |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Immunologic research Volume: 50 ISSN: 1559-0755 ISO Abbreviation: Immunol. Res. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-07-20 Completed Date: 2011-11-02 Revised Date: 2011-12-23 |
Medline Journal Info:
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Nlm Unique ID: 8611087 Medline TA: Immunol Res Country: United States |
Other Details:
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Languages: eng Pagination: 248-54 Citation Subset: IM |
Affiliation:
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Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Monoclonal
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pharmacology* Antibody-Dependent Cell Cytotoxicity / immunology Antigens, Neoplasm / immunology* Antineoplastic Agents / pharmacology* Dendritic Cells* / drug effects, immunology, metabolism Humans Immunity, Cellular / immunology Killer Cells, Natural* / drug effects, immunology, metabolism Neoplasms* / immunology, metabolism T-Lymphocytes / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Antigens, Neoplasm; 0/Antineoplastic Agents |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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