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AK7-deficiency reversal inhibits ccRCC progression and boosts anti-PD1 immunotherapy sensitivity.
- Source :
-
Aging [Aging (Albany NY)] 2024 Jul 05; Vol. 16 (13), pp. 11072-11089. Date of Electronic Publication: 2024 Jul 05. - Publication Year :
- 2024
-
Abstract
- Clear cell renal cell carcinoma (ccRCC) is a common kidney cancer with subtle early symptoms, high recurrence rates, and low sensitivity to traditional treatments like radiotherapy and chemotherapy. Identifying novel therapeutic targets is critical. The expression level of adenylate kinases 7 (AK7) in ccRCC was examined by the TCGAportal and UALCAN databases. The effect of AK7 on proliferation, invasion and migration of ccRCC cell lines was evaluated by cell assay. The correlation between AK7 expression and prognosis, as well as its direct relationship with immunotherapy efficacy, was analyzed using CANCERTOOL and Kaplan-Meier plotter data. Moreover, the TISIDB database was used to study the relationship between AK7 and immune markers. The effect of overexpressed AK7 combined with PD1 monoclonal antibody on ccRCC was evaluated in animal experiments. The results showed that low level of AK7 expression was observed in ccRCC tissues. The expression of AK7 can regulate the proliferation, invasion, and migration of human ccRCC cell lines. The level of AK7 expression was associated with OS of ccRCC patients. This was potentially due to the negative connection between AK7 expression and CD8+ T cell depletion, indicating that immunotherapy might be less effective in individuals with low AK7 expression. Conversely, augmenting AK7 demonstrated an enhanced effectiveness of anti-PD1 therapy. The findings of our research strongly indicated that AK7 could serve as both a prognostic indicator and therapeutic target for patients with ccRCC. Moreover, the overexpression of AK7 combined with anti-PD1 held promising potential as a therapeutic approach for treating ccRCC.
- Subjects :
- Humans
Cell Line, Tumor
Animals
Mice
Cell Proliferation drug effects
Cell Movement
Immune Checkpoint Inhibitors pharmacology
Immune Checkpoint Inhibitors therapeutic use
Disease Progression
Prognosis
Female
Male
Gene Expression Regulation, Neoplastic
Xenograft Model Antitumor Assays
Kidney Neoplasms immunology
Kidney Neoplasms therapy
Kidney Neoplasms pathology
Kidney Neoplasms genetics
Carcinoma, Renal Cell therapy
Carcinoma, Renal Cell immunology
Carcinoma, Renal Cell genetics
Carcinoma, Renal Cell pathology
Carcinoma, Renal Cell metabolism
Programmed Cell Death 1 Receptor metabolism
Programmed Cell Death 1 Receptor antagonists & inhibitors
Immunotherapy methods
Subjects
Details
- Language :
- English
- ISSN :
- 1945-4589
- Volume :
- 16
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Aging
- Publication Type :
- Academic Journal
- Accession number :
- 38970774
- Full Text :
- https://doi.org/10.18632/aging.206006