ANO9 regulates PD‐L2 expression and binding ability to PD‐1 in gastric cancer

Autor: Michihiro Kudou, Shuhei Komatsu, Tomohiro Arita, Keita Katsurahara, Hirotaka Konishi, Hiroki Shimizu, Atsushi Shiozaki, Eigo Otsuji, Takeshi Kubota, Kazuma Okamoto, Toshiyuki Kosuga, Eiichi Konishi, Mitsuo Kishimoto, Hitoshi Fujiwara
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Cancer Research
immune checkpoint blockage
Programmed Cell Death 1 Receptor
Apoptosis
Basic and Clinical Immunology
0302 clinical medicine
Phospholipid Transfer Proteins
Immune Checkpoint Inhibitors
Gene knockdown
medicine.diagnostic_test
Chemistry
Stomach
General Medicine
Prognosis
ANO9
Gene Expression Regulation
Neoplastic
Survival Rate
Oncology
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Immunohistochemistry
Original Article
Female
Anoctamins
Flow cytometry
03 medical and health sciences
Gastrectomy
Stomach Neoplasms
Cell Line
Tumor
Biomarkers
Tumor
medicine
Humans
Aged
Cell Proliferation
Microarray analysis techniques
gastric cancer
PD‐1
Cancer
Original Articles
Programmed Cell Death 1 Ligand 2 Protein
medicine.disease
Immune checkpoint
030104 developmental biology
Cell culture
PD‐L2
Cancer cell
Cancer research
Interferons
Follow-Up Studies
Zdroj: Cancer Science
ISSN: 1349-7006
1347-9032
Popis: The function of ANO9 in gastrointestinal cancer remains unclear. We investigated the biological behaviors and clinical prognostic values of ANO9 in gastric cancer (GC). Knockdown experiments were performed on human GC cell lines using ANO9 siRNA. Eighty‐four primary tissue samples from patients with advanced GC were examined immunohistochemically (IHC). Knockdown of ANO9 reduced the progression of cancer cells in MKN7 and MKN74 cells. A microarray analysis revealed that ANO9 regulated PD‐L2 via interferon (IFN)‐related genes. We confirmed using flow cytometry that the depletion of ANO9 reduced the binding ability to PD‐1 by downregulating the expression of PD‐L2 in MKN7 and MKN74 cells. IHC revealed a correlation between the expression of ANO9 and PD‐L2 and also that the strong expression of ANO9 was an independent poor prognostic factor in patients with advanced GC. The present results indicate that ANO9 regulates PD‐L2 and binding ability to PD‐1 via IFN‐related genes in GC. Therefore, ANO9 has potential as a biomarker and target of immune checkpoint blockage (ICB) for GC.
The depletion of ANO9 reduced the binding ability to PD‐1 by downregulating the expression of PD‐L2 in GC cells. This is the first report to clarify the mechanism of ANO9 regulating the immune escape of cancer cells via PD‐L2.
Databáze: OpenAIRE
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