Aldehyde Dehydrogenese-1 High Cancer Stem-like Cells/Cancer-initiating Cells Escape from Cytotoxic T Lymphocytes due to Lower Expression of Human Leukocyte Antigen Class 1.
In: Anticancer research, Jg. 44 (2024-05-01), Heft 5, S. 1877
academicJournal
Zugriff:
Background/aim: Human gastric cancer stem-like cells (CSCs)/cancer-initiating cells can be identified as aldehyde dehydrogenase-high (ALDH high ) cells. Cancer immunotherapy employing immune checkpoint blockade has been approved for advanced gastric cancer cases. However, the effectiveness of cancer immunotherapy against gastric CSCs/CICs remains unclear. This study aimed to investigate the susceptibility of gastric CSCs/CICs to immunotherapy.
Materials and Methods: Gastric CSCs/CICs were isolated as ALDH high cells using the human gastric cancer cell line, MKN-45. ALDH high clone cells and ALDH low clone cells were isolated using the ALDEFLUOR assay. ALDH1A1 expression was assessed via qRT-PCR. Sphere-forming ability was evaluated to confirm the presence of CSCs/CICs. A model neoantigen, AP2S1, was over-expressed in ALDH high clone cells and ALDH low clone cells, and susceptibility to AP2S1-specific TCR-T cells was assessed using IFNγ ELISPOT assay.
Results: Three ALDH high clone cells were isolated from MKN-45 cells. ALDH high clone cells exhibited a stable phenotype in in vitro culture for more than 2 months. The High-36 clone cells demonstrated the highest sphere-forming ability, whereas the Low-8 cells showed the lowest sphere-forming ability. High-36 cells exhibited lower expression of HLA-A24 compared to Low-8 cells. TCR-T cells specific for AP2S1 showed lower reactivity to High-36 cells compared to Low-8 cells.
Conclusion: High-36 cells and Low-8 cells represent novel gastric CSCs/CICs and non-CSCs/CICs, respectively. ALDH high CSCs/CICs evade T cells due to lower expression of HLA class 1.
(Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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Aldehyde Dehydrogenese-1 High Cancer Stem-like Cells/Cancer-initiating Cells Escape from Cytotoxic T Lymphocytes due to Lower Expression of Human Leukocyte Antigen Class 1.
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Autor/in / Beteiligte Person: | Shirosaki, T ; Kawai, N ; Ebihara, Y ; Murai, A ; Kubo, T ; Morita, R ; Murata, K ; Kanaseki, T ; Tsukahara, T ; Shichinohe, T ; Hirohashi, Y ; Hirano, S ; Torigoe, T |
Zeitschrift: | Anticancer research, Jg. 44 (2024-05-01), Heft 5, S. 1877 |
Veröffentlichung: | Attiki, Greece : International Institute of Anticancer Research ; <i>Original Publication</i>: Athens, Greece : Potamitis Press, 2024 |
Medientyp: | academicJournal |
ISSN: | 1791-7530 (electronic) |
DOI: | 10.21873/anticanres.16989 |
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