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ABSTRACT
Background
Immunotherapy has shown intracranial efficacy in non-small cell lung cancer (NSCLC) patients with brain metastases. However, predictive biomarkers for intracranial response to immunotherapy are lacking. This post-hoc analysis aimed to explore the potential of immunological cytokines in cerebrospinal fluid (CSF) to predict intracranial tumor response to immunotherapy in patients with brain metastases.
Methods
Treatment-naive NSCLC patients with brain metastases who received camrelizumab plus chemotherapy were enrolled. Paired plasma and CSF samples were prospectively collected at baseline and the first treatment assessment. All samples were analyzed for 92 immuno-oncology cytokines using Olink’s panels.
Results
A total of 28 patients were included in this analysis. At baseline, most immunological cytokines were significantly lower in CSF than in plasma, whereas a subset comprising CD83, PTN, TNFRSF21, TWEAK, ICOSLG, DCN, IL-8, and MCP-1, was increased in CSF. Baseline CSF levels of LAMP3 were significantly higher in patients with intracranial tumor response, while the levels of CXCL10, IL-12, CXCL11, IL-18, TIE2, HGF, and PDCD1 were significantly lower. Furthermore, the CXCL10, CXCL11, TIE2, PDCD1, IL-18, HGF, and LAMP3 in CSF were also significantly associated with intracranial progression-free survival for immunotherapy. The identified cytokines in CSF were decreased at the first treatment evaluation in patients with intracranial tumor response. The logistic CSF immuno-cytokine model yielded an AUC of 0.91, as compared to PD-L1 expression (AUC of 0.72).
Conclusions
Immunological cytokines in CSF could predict intracranial tumor response to immunotherapy in NSCLC patients with brain metastases, and the findings warrant validation in a larger prospective cohort study.
Trial registration
ClinicalTrials.gov identifier: NCT04211090.
Acknowledgments
We would like to thank the patients and family members who gave their consent to present the data in this study, as well as the investigators and research staff involved in this study.
Disclosure statement
No potential conflict of interest was reported by the authors.
List of Abbreviations
| CSF | = | cerebrospinal fluid |
| ICIs | = | immune checkpoint inhibitors |
| ORR | = | objective response rate |
| PFS | = | progression-free survival |
| OS | = | overall survival |
| CNS | = | central nervous system |
| NSCLC | = | non-small cell lung cancer |
| DCB | = | durable clinical benefit |
| MRI | = | magnetic resonance imaging |
| ROC | = | receiving operating curve |
| AUC | = | area under curve |
| ECOG PS | = | Eastern Cooperative Oncology Group performance status |
| LOD | = | limit of detection |
Ethics approval and consent to participate
This study was approved by the Ethics Committee of the Guangdong Association Study of Thoracic Oncology (GASTO ID:1060, Approval No. A2020–004). Written consent was obtained from all patients.
Author contributions
Dr. Likun Chen had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis.
Conception and study design: Meichen Li, Xie Dan and Likun Chen.
Patient recruitment and enrollment: Meichen Li, Xue Hou, Jing Chen, Baishen Zhang, Honghua Jiang, and Likun Chen.
Data acquisition and curation: Meichen Li.
Data analysis and interpretation: All authors.
Manuscript draft writing: Meichen Li.
Critical revision: Meichen Li, Dan Xie and Likun Chen.
Study supervision: Dan Xie and Likun Chen.
Availability of data and material
Dr. Chen had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2290790.