Abstract 379P
Background
T cell exhaustion describes a hypofunctional state characterized by progressive loss of T cell effector functions and is considered a pathway of resistance for cellular immunotherapies. However, little is known about the prognostic value of T cell exhaustion in patient who do not receive immunotherapy. In this study, we aimed to investigate the prognostic significance of T-cell exhaustion in non-immunotherapy treated oligometastatic LUAC with brain metastases by performing a comprehensive mRNA expression-based immune profiling.
Methods
Patients with synchronous or metachronous oligometastatic LUAC and brain metastases (BM) who underwent local ablative treatment including surgical resection of the primary tumor between 2008 and 2018 were retrospectively identified. No immunotherapy was given over the course of treatment. After total RNA isolation from specimens of the primary tumor, a digital gene expression analysis was performed using the NanoString nCounter platform. To assess the status of T-cell exhaustion, CD83 and CXCL13 were used as markers for precursor exhausted T cells (TPEX).
Results
Digital gene expression analysis was performed on 36 patients with histologically confirmed oligometastatic LUAC and BM (median age 62 (IQR 55–67) years and 58% male). Median Overall survival (OS) from BM diagnosis was 46 months (IQR 22–67). In the CD83 high group (cutoff 1463), median OS was significantly longer with 103 (95% CI 34 - NR) months in comparison to 36 (95% CI 34–63) months in the CD83 low group (HR 4.04 (95% CI: 1.55–10.5), p=0.002). Similarly, median OS was longer in the CXCL13 high group with 81 months (95% CI 36 - NR) months in contrast to the CXCL13 low group with 32 months (95% CI 14 – NR), (HR 2.89 (95% CI: 1.21–6.92), p=0.013).
Conclusions
The findings of this study suggest that also in non-immunotherapy-treated patients with oligometastatic LUAC, precursor T cell exhaustion may be a prognostic parameter, supporting the evidence from other cancer entities that T cell exhaustion reflects poor cancer control. Approaches to mitigate terminal T cell exhaustion by targeting the CXCL13/CXCR5-axis and downstream molecules may be promising in the field of oligometastatic LUAC.
Legal entity responsible for the study
A. Soltermann
Funding
SAKF, Stiftung fu?r angewandte Krebsforschung Zu?rich
Disclosure
R.S. Werner: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, BMS. I. Schmitt-Opitz: Financial Interests, Institutional, Research Grant: Roche, Medtronic, XVIVO; Financial Interests, Institutional, Advisory Board: AstraZeneca, MSD, BMS, Medtronic, Regeneron; Financial Interests, Institutional, Invited Speaker: Intuitive, Sanofi, Siemens, Astellas. All other authors have declared no conflicts of interest.