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Rescuing defective tumor-infiltrating T-cell proliferation in glioblastoma patients
Song Han1, Enlong Ma2, Xiaonan Wang2
1Department of Neurosurgery, General Hospital of Shenyang Military Area Command of the Chinese People's Liberation Army, Shenyang, Liaoning 110016, P.R. China.
Abstract:
Primary glioblastoma (GBM) is the most prevalent brain cancer, with fast progression and a poor prognosis. Current treatment options are unable to fully manage GBM since it is highly resistant to radiation and chemotherapy, and it cannot be completely removed by surgery. Thus, immunotherapeutic strategies utilizing tumor-infiltrating T cells have been investigated. In the present study, the T-cell response in GBM patients was examined in resected tumor samples and peripheral blood samples by flow cytometry. It was found that tumor-infiltrating T cells represented a rare population in all tumor cells, and were more refractory to anti-cluster of differentiation 3 (CD3) stimulation than their peripheral blood counterparts. A number of strategies were then assessed to boost tumor-infiltrating T-cell proliferation, and it was found that pre-incubation with 20 U/ml interleukin (IL)-2, as well as sequestration of IL-10 in culture, improved tumor T-cell proliferation following anti-CD3 stimulation. The stimulation of blood antigen-presenting cells by lipopolysaccharide, however, did not improve tumor T-cell proliferation. Overall, the present results provided a viable strategy for improving tumor-infiltrating CD3+ T-cell responses in GBM patients.
Insights
Glioblastoma T-cells are rare and resistant to stimulation. Interleukin-2 (IL-2) and IL-10 sequestration can enhance T-cell responses in glioblastoma patients, offering a potential immunotherapy strategy.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Research
Background:
- Glioblastoma (GBM) is an aggressive brain cancer with poor prognosis.
- Current treatments for GBM are limited due to resistance to radiation, chemotherapy, and surgical removal.
- Immunotherapy using tumor-infiltrating T cells is being explored for GBM treatment.
Purpose of the Study:
- To investigate the T-cell response in glioblastoma patients.
- To identify strategies for enhancing the proliferation of tumor-infiltrating T cells.
Main Methods:
- Flow cytometry was used to analyze T-cell populations in resected tumor and peripheral blood samples from GBM patients.
- Various methods were tested to stimulate and enhance T-cell proliferation in vitro.
Main Results:
- Tumor-infiltrating T cells were found to be a rare population and less responsive to anti-cluster of differentiation 3 (CD3) stimulation compared to peripheral blood T cells.
- Pre-incubation with interleukin-2 (IL-2) and IL-10 sequestration in culture significantly improved tumor T-cell proliferation after anti-CD3 stimulation.
- Stimulation of blood antigen-presenting cells with lipopolysaccharide did not enhance tumor T-cell proliferation.
Conclusions:
- Tumor-infiltrating CD3+ T-cell responses in glioblastoma patients can be improved.
- Interleukin-2 (IL-2) and IL-10 modulation represent a viable strategy for enhancing T-cell-based immunotherapy in GBM.
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