Rescuing defective tumor-infiltrating T-cell proliferation in glioblastoma patients

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.