PD-L1 and IL17 expression in tumor infiltrating lymphocytes are opposite prognostic factors in glioblastoma

Background

Glioblastoma (GB) is the most frequent malignant primary brain tumor. Median overall survival (OS) is only 15 months despite recent progress with the association of temozolomide and radiotherapy. Tumor infiltrating lymphocytes (TIL) are present in GB stroma but their influence on prognosis is not clearly defined. The purpose of this retrospective study was to explore the prognostic value in GB of tumor infiltration by IL17 (interleukin 17), CD45 and PD-L1 (programmed death ligand 1) expressing lymphocytes.

Methods

All included patients had surgery followed by radiotherapy and temozolomide (Stupp's regimen). IL-17, CD45 and PD-L1 were assessed by immunohistochemistry in a cohort of 77 GBM. Number of positive cells were count in a X40 field. We used the software cutoff finder to determine the optimal cut off to separate patients with high or low infiltrate. Logrank analysis and Cox proportional hazard models were used to determine overall survival factors in function of type and number of TIL.

Results

In univariate analysis, high number of IL17 expressing cells was correlated with poor OS (HR = 1.7 IC[1.1-1.19]p = 0.03). High PD-L1 infiltration was correlated with a better prognosis (OS : 15.3 months if PD-L1  1%; p = 0.05). IN contrast CD45 is no associated with outcome. In multivariate analysis, high PD-L1 infiltration remain independent factor was associated with a better survival (HR = 0.4 IC95 [0.2-0.8] p = 0.016) and high IL17 infiltration of poor survival ( HR = 2.6 IC95 [1.4-5.3] p = 0.03).

Conclusions

This study underline that PDL1 infiltrate and IL-17 are associated with outcome in a cohort of 77 patients with GBM that received an optimal treatment with surgery and radiochemotherapy. Such data support rational to test PD-L1 and IL17 targeted immunotherapy in GBM.

Clinical trial identification

Legal entity responsible for the study

Centre Georges Francçois Leclerc, Dijon, CHU Amiens

Funding

CHU Amiens

Disclosure

All authors have declared no conflicts of interest.