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 understood1. 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 cdr22,
3,
this humoral response has not been shown to be pathogenic3,
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.
