Abstract 1304P
Background
Cytokines have been reported to regulate immunological response. Hence, elucidating the determinative cytokines of response to immune-checkpoint inhibitors (ICIs) is key to improving outcomes and developing new treatment strategies.
Methods
This investigation of the relationship between baseline plasma levels of cytokines and clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with ICIs was used the multi-analyte flow assay. Furthermore, the predictive performance of candidate cytokine biomarkers in baseline plasma and tumor tissues were confirmed via ELISA and immunohistochemistry, respectively. In addition, the role and mechanism of the candidate cytokines in predicting response and promoting resistance to immunotherapy was explored.
Results
Based on our cohort of 48 NSCLC patients, circulating cytokines analysis revealed that baseline plasma level of interleukin-6 (IL-6) was higher in patients with progressive disease (p=0.04). We then identified that the baseline levels of IL-6 were remarkably upregulated in plasma samples (p=0.0039) and tumor tissues (p=0.0018) of NSCLC patients with progressive disease. Multivariate Cox regression analyses revealed that baseline IL-6 level was an independent prognostic predictor. In addition, a positive correlation between IL-6 and PD-L1 expression and a negative correlation between IL-6 and CD8+ T cells was observed in the tumor tissues. The vitro studies shown that IL-6 upregulated PD-L1 expression via the IL-6-JAK/Stat3 signaling pathways in tumor cells. The vivo studies suggested that IL-6 and PD-L1 antibody blockade combination therapy reduced tumor progression in murine models of NSCLC. Further analysis revealed that targeting IL-6 may enhance the efficacy of ICIs by improving the phenotypic properties and infiltration of CD8+ T cells.
Conclusions
This study elucidated that baseline plasma level of IL-6 may emerge as a powerful predictive tool for immunotherapy. Meanwhile, our results reveal that targeted inhibition of IL-6 may enhance the efficacy of anti-PD-L1 in NSCLC, which paves the way for the progress of IL-6 as a therapeutic target for cancer treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.