Abstract B082: PD-1 to CD8 ratio on tumor-infiltrating lymphocytes and peripheral blood mononuclear cells as a predictor for determining response of glioblastoma patients to radiation-induced ICD-based DC vaccine therapy
Authors: Lin Fang-Yu , Jan Chia-Ing , Tsai Wan-Chen , Harn Horng-Jyh , Lu Hsin-Man , Liu Ming-Chao , Chiu Shao-Chih , Cho Der-Yang 
Published: February 2019

Glioblastoma multiforme (GBM) is the most common and aggressive glioma within the central nervous system in adults. Radiation-induced ICD-based DC vaccine (RICD-DC vaccine) therapy plus conventional multi-modal regimen for GBM has been demonstrated with promising outcomes in clinical trials. However, some GBM patients received RICD-DC vaccine therapy did not increased survival rates than other GBM patients who only received conventional therapy. To investigate this issue, we conducted a retrospective study to analyze clinical and laboratory data to evaluate the factors which is critical for affecting the response rate of RICD-DC vaccine treatment. Patients with de novo GBM were enrolled (n=47) and divided into two subgroups: the first subgroup received post-surgical adjuvant immunotherapy with autologous RICD-DC vaccine (n=27) and the second received conventional treatment without immunotherapy (control, n=20). Quantitative immunohistochemistry for CD45, CD4, CD8, programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) was performed on patient tumor samples and peripheral blood mononuclear cells (PBMCs) at initial resection/biopsy before treatment. Pearson’s correlation, Cox proportional hazard model, and Kaplan-Meier analyses were performed to examine the correlations between these biomarkers expression and survival rates. In the RICD-DC vaccine group, patients with a lower PD-1+/CD8+ ratio (≤0.21) on tumor infiltrating lymphocytes (TILs) had longer overall survival (OS) (median 60.97 months, P &lt; 0.001) than patients with a higher PD-1+/CD8+ ratio (median 20.07 months, , P &lt; 0.001); 80% of the patients with a lower PD-1+/CD8+ ratio survived longer than 2 years whereas only 20% of patients with a higher PD-1+/CD8+ ratio. Similar results were observed in progression-free survival (PFS). Consistently, lymphocyte counts with lower PD-1+/CD8+ ratio (≤0.197) had much longer OS and PFS in patients’ PBMCs. In addition, there was a significant correlation of PD-1+/CD8+ ratio between TILs and PBMCs (Pearson’s correlation R2 = 0.6002, P &lt; 0.001). By contrast, OS and PFS did not be impacted by CD4−, CD8−, but PD-1+, CD45+ TILs (P = 0.073 and P = 0.249, respectively). Moreover, the significant prognostic factors of OS and PFS also contained younger age (&lt;57 years), gross total resection, and conventional treatment of concomitant chemoradiotherapy (CCRT) and PD-1+ lymphocyte counts in the RICD-DC vaccine group. In contrast to other factors, gender, counts of CD45+, CD4+ or CD8+ lymphocytes, tumoral PD-L1 expression, isocitrate dehydrogenase 1 mutation, and methylation status of O6 methylguanine-DNA methyltransferase promoter have no impact in both groups. Taken together, we found that TILs or PBMCs with lower PD-1+/CD8+ ratio in GBM patients with younger age, with gross tumor resection may be the desirable candidates who can be benefited from conventional multimodal regimen plus RICD-DC vaccine immunotherapy.

Citation Format: Fang-Yu Lin, Chia-Ing Jan, Wan-Chen Tsai, Horng-Jyh Harn, Hsin-Man Lu, Ming-Chao Liu, Shao-Chih Chiu, Der-Yang Cho. PD-1 to CD8 ratio on tumor-infiltrating lymphocytes and peripheral blood mononuclear cells as a predictor for determining response of glioblastoma patients to radiation-induced ICD-based DC vaccine therapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B082.