Tumor-specific killer cells in paraneoplastic cerebellar degeneration

Models for immune-mediated tumor regression in mice have defined an essential role for cytotoxic T lymphocytes (CTLs); however, naturally occurring tumor immunity in humans is poorly understood 1 . Patients with paraneoplastic cerebellar degeneration (PCD) provide an opportunity to explore the mecha...

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Bibliographic Details
Published in:Nature Medicine Vol. 4; no. 11; pp. 1321 - 1324
Main Authors: Albert, Matthew L., Darnell, Jennifer C., Bender, Armin, Francisco, Loise M., Bhardwaj, Nina, Darnell, Robert B.
Format: Journal Article Magazine Article
Language:English
Published: New York Nature Publishing Group US 01.11.1998
Nature Publishing Group
Subjects:
Animals
Apoptosis - radiation effects
Biomedical and Life Sciences
Biomedicine
Breast Neoplasms - immunology
Cancer Research
Cells, Cultured
Cerebellar Diseases - immunology
Cytotoxicity, Immunologic
Female
HeLa Cells
Histocompatibility Antigens Class I - immunology
Humans
Immunity, Cellular
Immunology
Infectious Diseases
Killer Cells, Natural - immunology
Life Sciences
Lymphoid Tissue - immunology
Metabolic Diseases
Mice
Molecular Medicine
Nerve Degeneration - immunology
Neurosciences
Ovarian Neoplasms - immunology
Paraneoplastic Syndromes - immunology
T-Lymphocyte Subsets - immunology
T-Lymphocytes, Cytotoxic - immunology
Ultraviolet Rays
ISSN:1078-8956, 1546-170X, 1744-7933
Online Access:Get full text
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Summary:Models for immune-mediated tumor regression in mice have defined an essential role for cytotoxic T lymphocytes (CTLs); however, naturally occurring tumor immunity in humans is poorly understood 1 . Patients with paraneoplastic cerebellar degeneration (PCD) provide an opportunity to explore the mechanisms underlying tumor immunity to breast and ovarian cancer. Although tumor immunity and autoimmune neuronal degeneration in PCD correlates with a specific antibody response to the tumor and brain antigen cdr2 2 , 3 , this humoral response has not been shown to be pathogenic 3 , 4 . Here we present evidence for a specific cellular immune response in PCD patients. We have detected expanded populations of MHC class I-restricted cdr2-specific CTLs in the blood of 3/3 HLA-A2.1 + PCD patients, providing the first description, to our knowledge, of tumor-specific CTLs using primary human cells in a simple recall assay. Cross-presentation of apoptotic cells by dendritic cells also led to a potent CTL response. These results indicate a model whereby immature dendritic cells that engulf apoptotic tumor cells can mature and migrate to draining lymph organs where they could induce a CTL response to tissue-restricted antigens. In PCD, peripheral activation of cdr2-specific CTLs is likely to contribute to the subsequent development of the autoimmune neuronal degeneration.
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ISSN:1078-8956
1546-170X
1744-7933
DOI:10.1038/3315