Related Experiment Video
Updated: Jun 10, 2025
Patient-Derived Tumor Explants As a "Live" Preclinical Platform for Predicting Drug Resistance in Patients
Published on: February 7, 2021
CD34 as a potential prognostic indicator for camrelizumab response in advanced non-small-cell lung cancer: insights
Xinyi Huang1, Baoqing Tian1, Ziyuan Ren1,2
1Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Background:
Given that only a small subset of patients with advanced non-small-cell lung cancer (aNSCLC) benefit from immune checkpoint inhibitors (ICIs), the effectiveness of ICIs is often compromised by the complex interplay within the tumor microenvironment (TME).
Objectives:
To identify predictive biomarkers associated with ICI resistance at a multi-omics spatial level.
Design:
A total of eight aNSCLC patients who received first-line anti-programmed cell death protein-1 (PD-1) monoclonal antibody camrelizumab at Shandong Cancer Hospital and Institute between 2021 and 2022 were included in the discovery cohort. An additional validation cohort of 45 samples from camrelizumab-treated aNSCLC patients was also enrolled.
Methods:
NanoString GeoMx® digital spatial profiling was conducted at the transcriptomic and proteomic level within pan-cytokeratin (panCK+), CD45+, and CD68+ compartments. For validation, multiplex immunofluorescence (mIF) staining was performed.
Results:
Distinct spatial expression patterns and levels of immune infiltration were observed between tumor and leukocyte compartments. Higher CD34 expression in the macrophage compartment correlated with poorer prognosis and response to camrelizumab (p < 0.05). mIF validation confirmed the association of elevated CD34 expression level with reduced progression-free survival (PFS; hazard ratio (HR) = 5.011, 95% confidence interval: 1.057-23.752, p = 0.042), outperforming traditional tumor markers in predictive accuracy.
Conclusion:
Our findings identify CD34 as a novel spatial biomarker for anti-PD-1 therapy efficacy, potentially guiding the selection of aNSCLC patients who are more likely to benefit from ICI treatment.
Trial Registration:
ChiCTR2000040416.
Insights
CD34 expression in macrophages predicts response to immune checkpoint inhibitors in advanced non-small-cell lung cancer. This finding may help select patients for anti-PD-1 therapy.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Immune checkpoint inhibitors (ICIs) benefit only a subset of advanced non-small-cell lung cancer (aNSCLC) patients.
- The tumor microenvironment (TME) complexity often compromises ICI effectiveness.
Purpose of the Study:
- To identify predictive biomarkers for ICI resistance using multi-omics spatial analysis.
- To evaluate CD34 as a potential spatial biomarker for anti-PD-1 therapy efficacy in aNSCLC.
Main Methods:
- NanoString GeoMx® digital spatial profiling (transcriptomic and proteomic) in tumor and immune cell compartments.
- Multiplex immunofluorescence (mIF) for validation.
- Analysis of 8 aNSCLC patients (discovery) and 45 patients (validation) treated with camrelizumab.
Main Results:
- Distinct spatial expression patterns observed between tumor and leukocyte compartments.
- Elevated CD34 expression in macrophages correlated with poorer prognosis and response to camrelizumab (p<0.05).
- mIF confirmed CD34's association with reduced progression-free survival (HR=5.011, p=0.042), outperforming traditional markers.
Conclusions:
- CD34 is a novel spatial biomarker for predicting anti-PD-1 therapy efficacy.
- This biomarker may guide patient selection for ICI treatment in aNSCLC.
- Spatial multi-omics profiling offers insights into TME-driven ICI resistance.
