Patients with lung cancer and paraneoplastic Hu syndrome harbor HuD-specific type 2 CD8(+) T cells Journal Article
| Authors: | Roberts, W. K.; Deluca, I. J.; Thomas, A.; Fak, J.; Williams, T.; Buckley, N.; Dousmanis, A. G.; Posner, J. B.; Darnell, R. B. |
| Article Title: | Patients with lung cancer and paraneoplastic Hu syndrome harbor HuD-specific type 2 CD8(+) T cells |
| Abstract: | Paraneoplastic neurologic disorders (PNDs) offer an uncommon opportunity to study human tumor immunity and autoimmunity. In small cell lung cancer (SCLC), expression of the HuD neuronal antigen is thought to lead to immune recognition, suppression of tumor growth, and, in a subset of patients, triggering of the Hu paraneoplastic neurologic syndrome. Antigen-specific CTLs believed to contribute to disease pathophysiology were described 10 years ago in paraneoplastic cerebellar degeneration. Despite parallel efforts, similar cells have not been defined in Hu patients. Here, we have identified HuD-specific T cells in Hu patients and provided an explanation for why their detection has been elusive. Different Hu patients harbored 1 of 2 kinds of HuD-specific CD8(+) T cells: classical IFN-γ-producing CTLs or unusual T cells that produced type 2 cytokines, most prominently IL-13 and IL-5, and lacked cytolytic activity. Further, we found evidence that SCLC tumor cells produced type 2 cytokines and that these cytokines trigger naive CD8(+) T cells to adopt the atypical type 2 phenotype. These observations demonstrate the presence of an unusual noncytotoxic CD8(+) T cell in patients with the Hu paraneoplastic syndrome and suggest that SCLC may evade tumor immune surveillance by skewing tumor antigen-specific T cells to this unusual noncytolytic phenotype. |
| Keywords: | adult; controlled study; aged; human cell; case report; cisplatin; cancer combination chemotherapy; nonhuman; cd8+ t lymphocyte; animal cell; mouse; phenotype; animal tissue; etoposide; interleukin 13; interleukin 5; animal experiment; tumor antigen; lung small cell cancer; gamma interferon; cytotoxic t lymphocyte; tumor cell; cytokine production; cytolysis; immunosurveillance; hu antigen; paraneoplastic hu syndrome; paraneoplastic neuropathy |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 119 |
| Issue: | 7 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2009-07-01 |
| Start Page: | 2042 |
| End Page: | 2051 |
| Language: | English |
| PROVIDER: | scopus |
| PMCID: | PMC2701858 |
| PUBMED: | 19509467 |
| DOI: | 10.1172/jci36131 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 30 November 2010" - "CODEN: JCINA" - "Source: Scopus" |
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