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Supplementary Information from The Antigen ASB4 on Cancer Stem Cells Serves as a Target for CTL Immunotherapy of Colorectal Cancer

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posted on 2023-04-03, 23:20 authored by Sho Miyamoto, Vitaly Kochin, Takayuki Kanaseki, Ayumi Hongo, Serina Tokita, Yasuhiro Kikuchi, Akari Takaya, Yoshihiko Hirohashi, Tomohide Tsukahara, Takeshi Terui, Kunihiko Ishitani, Fumitake Hata, Ichiro Takemasa, Akihiro Miyazaki, Hiroyoshi Hiratsuka, Noriyuki Sato, Toshihiko Torigoe

Supplementary Information

Funding

JSPS

Suhara Kinen Zaidan

AMED

Ono Cancer Research Fund

Ministry of Education, Culture, Sports, Science and Technology of Japan

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ARTICLE ABSTRACT

Colorectal cancer consists of a small number of cancer stem cells (CSC) and many non-CSCs. Although rare in number, CSCs are a target for cancer therapy, because they survive conventional chemo- and radiotherapies and perpetuate tumor formation in vivo. In this study, we conducted an HLA ligandome analysis to survey HLA-A24 peptides displayed by CSCs and non-CSCs of colorectal cancer. The analysis identified an antigen, ASB4, which was processed and presented by a CSC subset but not by non-CSCs. The ASB4 gene was expressed in CSCs of colorectal cancer, but not in cells that had differentiated into non-CSCs. Because ASB4 was not expressed by normal tissues, its peptide epitope elicited CD8+ cytotoxic T-cell (CTL) responses, which lysed CSCs of colorectal cancer and left non-CSCs intact. Therefore, ASB4 is a tumor-associated antigen that can elicit CTL responses specific to CSCs and can discriminate between two cellular subsets of colorectal cancer. Adoptively transferred CTLs specific for the CSC antigen ASB4 could infiltrate implanted colorectal cancer cell tumors and effectively prevented tumor growth in a mouse model. As the cancer cells implanted in these mice contained very few CSCs, the elimination of a CSC subset could be the condition necessary and sufficient to control tumor formation in vivo. These results suggest that CTL-based immunotherapies against colorectal CSCs might be useful for preventing relapses. Cancer Immunol Res; 6(3); 358–69. ©2018 AACR.

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