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Unmasking of alpha-fetoprotein-specific CD4(+) T cell responses in hepatocellular carcinoma patients undergoing embolization.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Ayaru, Lakshmana Alisa, Akeel Pathan, Ansar Williams, Roger Davidson, Brian Meyer, Tim Behboudi, Shahriar |
| Copyright Year | 2007 |
| Abstract | Necrosis of tumor cells can activate both innate and adaptive antitumor immunity. However, there is little information on the effects of necrosis-inducing cancer treatments on tumor-specific T cell immune responses in humans. We studied the effects of a necrosis-inducing treatment (embolization) on anti-alpha-fetoprotein (AFP)-specific CD4(+) T cell responses in hepatocellular carcinoma (HCC) patients and controls using an array of AFP-derived peptides. In this study, we show that AFP-specific CD4(+) T cell responses to three immunodominant epitopes in HCC patients were significantly expanded during (p < 0.0001) and after embolization (p < 0.002). The development of higher frequencies of AFP-specific CD4(+) T cells after treatment were significantly associated with the induction of >50% necrosis of tumor and an improved clinical outcome (p < 0.007). In addition, we identified two novel HLA-DR-restricted AFP-derived CD4(+) T cell epitopes (AFP(137-145) and AFP(249-258)) and showed that the CD4(+) T cells recognizing these epitopes produce Th1 (IFN-gamma and TNF-alpha) but not Th2 (IL-5)-type cytokines. AFP(137-145)-, AFP(249-258)-, and AFP(364-373)-specific CD4(+) T cells were detected in HCC patients but not in patients with chronic liver diseases or healthy donors. In conclusion; our study shows that induction of tumor necrosis by a conventional cancer treatment can unmask tumor rejection Ag cell-mediated immunity and provides a rationale for combining embolization with immunotherapy in HCC patients. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/178/3/1914.full.pdf |
| PubMed reference number | 17237442v1 |
| Volume Number | 178 |
| Issue Number | 3 |
| Journal | Journal of immunology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adrenergic alpha-Agonists Biomarkers, Tumor Cellular Immunity Cellular Phone Deny (action) Embolization, Therapeutic Epitopes Epitopes, T-Lymphocyte Fetal Proteins Immunotherapy Leukemia, B-Cell Liver carcinoma Liver diseases Necrosis Neoplasms Patients alpha-Fetoproteins type I interferon receptor |
| Content Type | Text |
| Resource Type | Article |
