Predictors of Response to Autologous Dendritic Cell Therapy in Glioblastoma Multiforme.

BACKGROUND

Glioblastoma (GBM) is the most common and lethal primary malignant glioma in adults. Dendritic cell (DC) vaccines have demonstrated promising results in GBM clinical trials. However, some patients do not respond well to DC therapy, with survival rates similar to those of conventional therapy. We retrospectively analyzed clinical and laboratory data to evaluate the factors affecting vaccine treatment.

METHODS

Forty-seven patients with GBM were enrolled at China Medical University Hospital between 2005 and 2010 and divided into two subgroups. One subgroup of 27 patients received postsurgical adjuvant immunotherapy with autologous dendritic cell/tumor antigen vaccine (ADCTA) in conjunction with conventional treatment of concomitant chemoradiotherapy (CCRT) with temozolomide. The other 20 patients received only postsurgical conventional treatment without immunotherapy. Immunohistochemistry for CD45, CD4, CD8, programed death ligand 1 (PD-L1), and programed death 1 (PD-1) was performed on sections of surgical tumor specimens and peripheral blood mononuclear cells (PBMCs). Pearson's correlation, Cox proportional hazard model, and Kaplan-Meier analyses were performed to examine the correlations between the prognostic factors and survival rates.

RESULTS

Younger age (<57 years), gross total resection, and CCRT and PD-1 lymphocyte counts were significant prognostic factors of overall survival (OS) and progression-free survival (PFS) in the ADCTA group. Sex, CD45 lymphocyte count, CD4 or CD8 lymphocyte count, tumor PD-L1 expression, isocitrate dehydrogenase 1 mutation, and O6 methylguanine-DNA methyltransferase promoter methylation status were not significant factors in both groups. In the ADCTA group, patients with tumor-infiltrating lymphocytes (TILs) with a lower PD-1/CD8 ratio (≤0.21) had longer OS and PFS (median OS 60.97 months,  < 0.001 and PFS 11.2 months,  < 0.008) compared to those with higher PD-1/CD8 ratio (>0.21) (median OS 20.07 months,  < 0.001 and PFS 4.43 months,  < 0.008). Similar results were observed in patients' PBMCs; lymphocyte counts with lower PD-1/CD8 ratio (≤0.197) had longer OS and PFS. There was a significant correlation of PD-1/CD8 ratio between TILs and PBMCs (Pearson's correlation  = 0.6002,  < 0.001). By contrast, CD4, CD8, but PD-1, CD45 tumor-infiltrating lymphocytes have no impact on OS and PFS ( = 0.073 and  = 0.249, respectively).

CONCLUSION

For patients receiving DC vaccine adjuvant therapy, better outcomes are predicted in patients with younger age, with TILs or PBMCs with lower PD-1/CD8 ratio, with gross tumor resection, and receiving CCRT.