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Updated: Apr 5, 2026
In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
Comparative effect of two pan-class I PI3K inhibitors used as anticancer drugs on human T cell function
Belén Blanco1, Carmen Herrero-Sánchez1, Concepción Rodríguez-Serrano1
1Department of Hematology, Hospital Universitario de Salamanca/Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
Abstract:
The phosphatidylinositol 3-kinase (PI3K) pathway is commonly deregulated in cancer and, thus, PI3K has been recognized as an attractive molecular target for novel anti-cancer therapies. However, the effect of PI3K inhibitors on T-cell function, a key component of antitumor immunity, has been scantly explored. The objective of this study was to investigate the effect on human T-cell activation of two PI3K inhibitors currently being tested in clinical trials: PX-866 and BKM120. Their activity against a leukemic T cell line was also assessed. For that purpose, Jurkat cells or anti-CD3/anti-CD28 stimulated human peripheral blood mononuclear cells were cultured in the presence of different concentrations of PX-866 or BKM120 and their effect on T-cell proliferation, apoptosis, expression of activation markers and cytokine secretion was analyzed by flow cytometry. In addition, Akt and Erk phosphorylation was analyzed by Western blotting. Both PX-866 and BKM120 decreased viability of Jurkat cells and blocked cell cycle progression. Regarding primary T cells, both compounds similarly inhibited expression of activation markers and cytokine secretion, although they did not induce apoptosis of stimulated T cells. Interestingly, we found differences in their ability to block T-cell proliferation and IL-2 secretion, exerting BKM120 a more potent inhibition. These disparate effects could be related to differences observed in PI3K/Akt and RAS/MEK/ERK signaling between PX-866 and BKM120 treated cells. Our results suggest that, when selecting a PI3K inhibitor for cancer therapy, immunosuppressive characteristics should be taken into account in order to minimize detrimental effects on immune function.
Insights
Two PI3K inhibitors, PX-866 and BKM120, impact T-cell function. BKM120 more potently inhibits T-cell proliferation and IL-2 secretion, suggesting immunosuppressive effects should guide cancer therapy selection.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- The phosphatidylinositol 3-kinase (PI3K) pathway is frequently dysregulated in cancer, making PI3K inhibitors promising anti-cancer agents.
- The impact of PI3K inhibitors on T-cell function, crucial for anti-tumor immunity, remains under-explored.
Purpose of the Study:
- To investigate the effects of two clinical trial PI3K inhibitors, PX-866 and BKM120, on human T-cell activation.
- To assess the activity of these inhibitors against a T-cell leukemia line.
Main Methods:
- Human peripheral blood mononuclear cells and Jurkat cells were treated with PX-866 or BKM120.
- T-cell proliferation, apoptosis, activation markers, and cytokine secretion were analyzed via flow cytometry.
- Akt and Erk phosphorylation was assessed using Western blotting.
Main Results:
- Both PX-866 and BKM120 reduced Jurkat cell viability and cell cycle progression.
- Primary T cells showed inhibited activation marker expression and cytokine secretion, without induced apoptosis.
- BKM120 demonstrated more potent inhibition of T-cell proliferation and IL-2 secretion compared to PX-866.
Conclusions:
- PI3K inhibitors PX-866 and BKM120 affect T-cell activation and function.
- Differences in signaling pathways may explain varied effects on T-cell proliferation and IL-2 secretion.
- Immunosuppressive properties of PI3K inhibitors must be considered during cancer therapy selection to preserve immune function.
