Research Paper Volume 16, Issue 13 pp 11072—11089

AK7-deficiency reversal inhibits ccRCC progression and boosts anti-PD1 immunotherapy sensitivity

Yigang Jin1, *, , Minjie Chen2, *, , Fei Chen2, *, , Zhaofeng Gao2, , Xiaoping Li2, , Lingyu Hu2, , Dandan Cai1, , Siqi Zhao2, , Zhengwei Song2, ,

  • 1 Department of Urology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
  • 2 Department of Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
* Co-first authorship

Received: March 13, 2024       Accepted: June 3, 2024       Published: July 5, 2024
How to Cite

Copyright: © 2024 Jin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


ccRCC: Clear cell renal cell carcinoma; AK7: Adenylate kinases 7; PD1: Programmed Cell Death Protein 1; ICIs: Immune Checkpoint Inhibitors; PD-L1: Programmed death ligand-1; CTLA-4: Cytotoxic T-lymphocyte antigen-4; mTOR: Mammalian target of rapamycin; RTK: Receptor tyrosine kinase; ATP: Adenosine triphosphate; PCD: Primary ciliary dyskinesia; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; FBS: Fetal bovine serum; HPA: Human Protein Atlas; VEGF: Vascular endothelial growth factor; FDA: Food and Drug Administration; PDX: Patient-derived xenograft.