Cerebrospinal fluid immunological cytokines predict intracranial tumor response to immunotherapy in non-small cell lung cancer patients with brain metastases

Meichen Li; Jing Chen; Hui Yu; Baishen Zhang; Xue Hou; Honghua Jiang; Dan Xie; Likun Chen

doi:10.1080/2162402X.2023.2290790

Cerebrospinal fluid immunological cytokines predict intracranial tumor response to immunotherapy in non-small cell lung cancer patients with brain metastases

Oncoimmunology. 2023 Dec 7;13(1):2290790. doi: 10.1080/2162402X.2023.2290790. eCollection 2024.

Authors

Meichen Li^{1

2

3}, Jing Chen^{1

2

3}, Hui Yu^{1

2

3}, Baishen Zhang^{1

2

3}, Xue Hou^{1

2

3}, Honghua Jiang⁴, Dan Xie^{2

3

5}, Likun Chen^{1

2

3}

Affiliations

¹ Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
² State Key Laboratory of Oncology in South China, Guangzhou, China.
³ Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
⁴ Department of Oncology, Southern Theater Air Force Hospital, Guangzhou, China.
⁵ Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China.

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.

Keywords: Brain metastases; cerebrospinal fluid; immunological cytokines; immunotherapy; tumor response.

MeSH terms

Brain Neoplasms* / secondary
Brain Neoplasms* / therapy
Carcinoma, Non-Small-Cell Lung* / drug therapy
Cytokines
Humans
Immunotherapy
Interleukin-18 / therapeutic use
Lung Neoplasms* / drug therapy
Prospective Studies

Substances

Interleukin-18
Cytokines

Associated data

ClinicalTrials.gov/NCT04211090

Grants and funding

This study was supported by the National Natural Science Foundation of China under Grant [number 82072559]. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or decision to submit the manuscript for publication.