2058 - Digital Spatial Profiling of the Tumor Microenvironment in Patients with Advanced Non-Small Cell Lung Cancer Reveals Biomarkers of Response to Anti-PD1 Antibody

X. Huang, B. Tian, J. Yu, and D. Chen; Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China

Purpose/Objective(s): Given that only a small subset of patients with advanced non-small-cell lung cancer (aNSCLC) benefit from immune checkpoint inhibitors (ICIs), whereas the complexity of tumor microenvironment (TME) characteristics is an essential factor limiting immunotherapy efficacy. Here, we sought to find predictive biomarkers associated with ICIs resistance from the multi-omics spatial level.

Materials/

Methods: A total of 8 lung puncture tissue samples from aNSCLC patients treated with anti-PD-1 monoclonal antibody camrelizumab were analyzed using a multiplex analysis platform. 18000 RNA targets and 42 protein targets were used for spatial transcriptomics and proteomics detection in three tissue (panCK+, CD45+, and CD68+) compartments. Validation was performed by multiplex immunofluorescence (mIF) staining in an additional cohort with 45 aNSCLC patients who accepted camrelizumab.

Results: We found that the tumor and immune compartment in the TME showed different spatial expression patterns and immune infiltration abundance in aNSCLC patients. Subsequently, we found that patients with higher CD34 expression in the macrophage region had a worse prognosis and poorly response to camrelizumab (p<0.05). Using mIF in an independent camrelizumab treated aNSCLC cohort, we validated that CD34 levels in the macrophage compartment, but not in the tumor compartment, were associated with worse progression-free survival (PFS; HR=5.160, 95% CI: 1.209 to 22.026, p=0.012). Furthermore, CD34 exhibited stronger clinical predictive power compared with traditional tumor signatures.

Conclusion: Our study confirms CD34 as a novel indicative biomarker of anti-PD-1 therapy at a spatial level. This may help to choose subgroups of patients who may benefit from immunotherapy.