Carla S. Fogolin

Conference 2023 Live Talk

Talk title

Glioblastoma patients treated with allogeneic DC vaccination may have a shift in their DC’s allogeneic stimulation capacity after surgery

Authors and Affiliations

Carla Sanzochi Fogolin1, Gabriela Coeli Menezes Evangelista1, Elizabeth Alexandra Flatow1, Jaqueline Vaz de Oliveira1, Nadia Emely Chauca Torres1, Nataly Peres2, Mariana Pereira Pinho1, Patrícia Cruz Bergami-Santos1 and José Alexandre Marzagão Barbuto1,3

1. Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
2. Laboratory of Experimental Surgery (LIM-26), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil
3. Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Hematology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil.

Abstract

Background

Glioblastoma (GBM) is the most invasive, undifferentiated, aggressive, and common glioma in adults. The standard treatment, consisting of “maximum” surgical resection, followed by concomitant radiotherapy and chemotherapy, only reaches 15 months of median survival and, in many cases, patients experience low quality of life, which indicates the urgency of developing new therapeutic approaches. Immunotherapy approaches based on dendritic cells (DC) are good candidates, due to their ability to activate T lymphocytes. One of these approaches, now being tested to treat GBM, consists on using allogeneic DC to vaccinate the patients – substituting the potentially dysfunctional autologous DC. The DC are fused with tumor cells that provide the antigens and the autologous MHC context. This strategy has been shown to revert the dysfunctional state of the autologous DC in melanoma and renal cell carcinoma patients, enhancing their ability to activate CD4+ and CD8+ T lymphocytes.

Methods

To evaluate if this phenomenon was also true for GBM patients, allogeneic stimulation experiments were carried out, using lymphocytes from healthy donors and DC derived from monocytes (mo-DC) from GBM patients at various times: before surgery, after surgery and before each dose of the therapeutic vaccine. Also, we accessed blood test results from the patients during the months of vaccination and analyzed the granulocyte/lymphocyte ratio and the plateled/lymphocyte ratio, and their association with survival.

Results

The results demonstrate that there is large variability in the response of individual patients and among vaccine doses. An interesting phenomenon was frequently observed: there was a decline in the T lymphocytes stimulation, both of CD4+ and CD8+ after surgery, suggesting that tumor removal might be responsible for change in the immune status. Interestingly, frequently, the T cell stimulation increased after immunotherapy, around the 2nd and 4th month of vaccination, however this increase was not sustained. Likewise, the granulocyte/lymphocyte ratio of the patients tended to show an increase around the 2nd and 4th month of vaccination.

Conclusions

Thus, we show here that tumor removal and immunotherapy seem to change mo-DCs ability to induce T cell proliferation. Further studies will tell if the changes observed in the stimulation rate correlates with the patient’s clinical response.