The Lck protein (p56 lck ), a src family tyrosine kinase essential for T cell development and function, is aberrantly expressed in various types of cancers. We revealed recently that Lck can be a tumor antigen recognized by HLA-A24restricted and tumor-specific cytotoxic T lymphocytes (CTLs) of cance
HLA class-I-restricted and tumor-specific CTL in tumor-infiltrating lymphocytes of patients with gastric cancer
β Scribed by Tomoaki Hoshino; Naoko Seki; Megumi Kikuchi; Terukazu Kuramoto; Osamu Iwamoto; Issei Kodama; Kikuo Koufuji; Jinryo Takeda; Kyogo Itoh
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- French
- Weight
- 138 KB
- Volume
- 70
- Category
- Article
- ISSN
- 0020-7136
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β¦ Synopsis
Immune recognition of human cancers except melanoma is not well understood at either the cellular or the molecular level. We demonstrate in this study the existence of HLA class-I-restricted and tumor-specific CTL in IL-2-activated TIL (tumor-infiltrating lymphocytes) of all 4 gastric cancer patients tested. We established HLA A2-restricted and adenocarcinoma-specific CTL in 2 HLA A0201+ patients, and HLA A2402-restricted CTL recognizing both adenocarcinoma and squamous-cell carcinomas (SCC) in the 2 remaining HLA A2402+ patients. Further, HLA A3101-restricted and adenocarcinoma-specific CTL were established in 1 of the 2 HLA A2402+ patients who had HLA A3101 allele. HLA A2-, A2402- and A3101-restricted CD8+ CTL clones were established from these parental CTL lines. The 2 HLA A2-restricted CTL lines lysed 8 of 13 HLA A2+ adenocarcinoma cell lines established from different organs (stomach, colon, lung and breast) with different subtypes (HLA A0201, A0206 and A0207). The HLA A2-restricted CTL line recognized 9 and 6 different HPLC fractions of peptides eluted from the HLA A0201+ breast and HLA A0201+ colon adenocarcinoma cell lines, respectively. Allele-specific deletion of HLA A2 or A24 molecules was observed in some tumor lines that were not susceptible to lysis by the CTL lines. These results suggest that TIL of gastric cancer possess CTL recognizing different peptide antigens binding to different HLA-A alleles that are widely expressed on adenocarcinomas and also, to some extent, on SCC from different organs.
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Strategies to identify tumor-associated antigens rely on the paradigm that tumor-associated peptides presented in the context of HLA-class I are recognized by the cellular immune system. Approaches to isolate tumor-specific cytotoxic T lymphocytes (CTL) from tumor-infiltrating lymphocytes are diffic
## Abstract To identify CTLβdirected antigens in gastrointestinal cancer, we have investigated antigens recognized by the HLAβA2βrestricted CTL line established from T cells infiltrating into colon cancer and report herein cleavage and polyadenylation specificity factor (CPSF) as a potent antigen h