HLA class-I-restricted and tumor-specific CTL in tumor-infiltrating lymphocytes of patients with gastric cancer

Abstract

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 1 patients, and HLA A2402-restricted CTL recognizing both adenocarcinoma and squamous-cell carcinomas (SCC) in the 2 remaining HLA A2402 1 patients. Further, HLA A3101-restricted and adenocarcinoma-specific CTL were established in 1 of the 2 HLA A2402 1 patients who had HLA A3101 allele. HLA A2-, A2402-and A3101-restricted CD8 1 CTL clones were established from these parental CTL lines. The 2 HLA A2-restricted CTL lines lysed 8 of 13 HLA A2 1 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 1 breast and HLA A0201 1 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. Int.

Autologous Tumor‐specific Cytotoxic T Lymphocytes in a Patient with Lung Adenocarcinoma: Implications of the Shared Antigens Expressed in HLA‐A24 Lung Cancer Cells

“…The HLA-A haplotype of the patient was HLA-A2/A24, as described in "Materials and Methods." Interestingly, however, A110L expressed no HLA-A2 on the cell surface as judged from the flow cytometry analysis, although EBV-B from the patient expressed HLA-A2, as reported by Hoshino et al 19) in other cancer cell lines. Allele-specific deletion of HLA-A2 of A110L was confirmed by genotypic examination (Table II).…”

CD155T/TIGIT Signaling Regulates CD8+ T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer

“…Five-year survival rate of gastric cancer is lower than 30%, and the current therapeutic methods show little improvement for gastric cancer survival (2). Tumor-specific cytotoxic T cells are present in gastric cancer tissue, but are unable to contain tumors because of poor immune responses in the tumor microenvironment (3). Reversing this effect would be a potential therapeutic approach to enhance the effectiveness of current treatments.…”

Frequencies of HER‐2/neu overexpression relating to HLA haplotype in patients with gastric cancer

“…2 We and others reported that MHC class I-restricted cytotoxic-T lymphocytes (CTLs) from gastric-cancer patients can react specifically against autologous tumor cells. [3][4][5][6] Adoptive immunotherapy based on gastric cancer-specific CTLs, or vaccinations based on the MHC class I-associated tumor antigens that they recognize, represent alternative therapeutic approaches. The presence of tumor-associated antigens recognized by gastric-cancer-specific CTLs restricted by HLA-A31 6 or HLA-A2.1 molecules 4 has been demonstrated, although the nature of these antigens has not been defined.…”