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.

Shirosaki, T ; Kawai, N ; et al.

In: Anticancer research, Jg. 44 (2024-05-01), Heft 5, S. 1877

academicJournal

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.

Titel:	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.
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
Schlagwort:	Humans Cell Line, Tumor Retinal Dehydrogenase metabolism Tumor Escape immunology Histocompatibility Antigens Class I metabolism Histocompatibility Antigens Class I immunology Neoplastic Stem Cells metabolism Neoplastic Stem Cells immunology Neoplastic Stem Cells pathology Stomach Neoplasms immunology Stomach Neoplasms pathology Stomach Neoplasms metabolism Aldehyde Dehydrogenase 1 Family metabolism Aldehyde Dehydrogenase 1 Family genetics T-Lymphocytes, Cytotoxic immunology T-Lymphocytes, Cytotoxic metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Anticancer Res] 2024 May; Vol. 44 (5), pp. 1877-1883. MeSH Terms: Neoplastic Stem Cells* / metabolism ; Neoplastic Stem Cells* / immunology ; Neoplastic Stem Cells* / pathology ; Stomach Neoplasms* / immunology ; Stomach Neoplasms* / pathology ; Stomach Neoplasms* / metabolism ; Aldehyde Dehydrogenase 1 Family* / metabolism ; Aldehyde Dehydrogenase 1 Family* / genetics ; T-Lymphocytes, Cytotoxic* / immunology ; T-Lymphocytes, Cytotoxic* / metabolism ; Humans ; Cell Line, Tumor ; Retinal Dehydrogenase / metabolism ; Tumor Escape / immunology ; Histocompatibility Antigens Class I / metabolism ; Histocompatibility Antigens Class I / immunology Contributed Indexing: Keywords: ALDH1; Gastric cancer; HLA class 1; cancer stem cell; cytotoxic T lymphocytes Substance Nomenclature: EC 1.2.1 (Aldehyde Dehydrogenase 1 Family) ; EC 1.2.1.36 (Retinal Dehydrogenase) ; EC 1.2.1.36 (ALDH1A1 protein, human) ; 0 (Histocompatibility Antigens Class I) Entry Date(s): Date Created: 20240427 Date Completed: 20240427 Latest Revision: 20240522 Update Code: 20240522

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