Related Experiment Video
Updated: Apr 5, 2026
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
Over-expressing Akt in T cells to resist tumor immunosuppression and increase anti-tumor activity
Yanhong Wu1, Zhenling Deng2, Yishu Tang3
1Department of Immunology, Cancer Hospital & Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China. wuyanhong849@126.com.
Background:
Tumor employs various means to escape immunosurveillance and inhibit immune attack, and strategies have been developed to counteract the inhibitory signals. However, due to the complex suppressive mechanisms in the tumor microenvironment, blocking one or a few inhibitory signals has only limited effects on therapeutic efficacy. Instead of targeting tumor immunosuppression, we considered from another point of view, and hypothesized that manipulating T cells to make them resist any known or unknown suppressive mechanism may be more effective for cancer treatment.
Methods:
We used OT-1 cells transduced with retroviruses encoding Akt and human peripheral blood lymphocytes (PBLs) transduced with retroviruses encoding both Akt and a chimeric antigen receptor (CAR) specific for tumor antigen EpCAM to examine the effect of over-expressing Akt on tumor specific T cells in tumor environment.
Results:
We show that Akt activity of T cells in the tumor environment was inhibited, and over-expressing Akt in OT-1 cells increased the cytokine production and cell proliferation in the presence of B16-OVA tumor cells. What's more, adoptive transfer of OT-1 cells over-expressing Akt inhibited B16-OVA tumor growth and prolonged mouse survival. To examine if over-expressing Akt could increase the anti-tumor activity of T cells in human cancer, PBLs co-expressing EpCAM specific CAR and Akt were cultured with EpCAM-expressing human prostate cancer cells PC3M, and less inhibition on cell proliferation and less apoptosis were observed. In addition, adoptive transfer of PC3M specific T cells over-expressing Akt resulted in more dramatic tumor inhibitory effects in PC3M bearing NOD/SCID mice.
Conclusions:
These data indicates that over-expressing Akt in tumor specific T cells increases T cell proliferation and activity in the tumor environment, and enhances anti-tumor effects of adoptively transferred T cells. Our study provides a new strategy to improve the efficacy of adoptive T cell therapy, and serves as an important foundation for clinical translation.
Insights
Overexpressing Akt in T cells enhances their anti-tumor activity and resistance to the tumor microenvironment, improving adoptive T cell therapy efficacy for cancer treatment.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Tumors evade immune surveillance through complex suppressive mechanisms.
- Targeting single inhibitory signals in the tumor microenvironment has limited therapeutic effects.
- A novel strategy involves enhancing T cell resistance to suppressive mechanisms.
Purpose of the Study:
- To investigate the effect of overexpressing Akt on tumor-specific T cells within the tumor microenvironment.
- To determine if Akt manipulation can enhance T cell-mediated anti-tumor activity.
- To assess the potential of this strategy for improving adoptive T cell therapy.
Main Methods:
- Transduction of OT-1 cells and human peripheral blood lymphocytes (PBLs) with retroviruses encoding Akt.
- Engineering PBLs with a chimeric antigen receptor (CAR) specific for EpCAM.
- Evaluating T cell proliferation, cytokine production, and apoptosis in co-culture systems with tumor cells.
- Assessing tumor growth inhibition and survival in mouse models following adoptive T cell transfer.
Main Results:
- Overexpressing Akt increased cytokine production and proliferation of T cells in the presence of tumor cells.
- Adoptive transfer of Akt-overexpressing T cells inhibited tumor growth and prolonged survival in mouse models.
- Akt-overexpressing T cells demonstrated enhanced anti-tumor activity against human cancer cells in vitro and in vivo.
Conclusions:
- Overexpressing Akt enhances T cell activity and proliferation within the tumor microenvironment.
- This approach improves the anti-tumor effects of adoptively transferred T cells.
- This strategy offers a promising foundation for enhancing adoptive T cell therapy and clinical translation.
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