Abstract 6428: Transcriptome analysis of tissues and peripheral blood revealed potential biomarkers for chemo/radio-immunotherapy in non-small cell lung cancer
Authors: Hu Jing , Zhang Jianguo , Cheng Peng , Chen Yanhua , Zhu Changbin , Yi Feilin , Xie Conghua 
Published: March 2024

Abstract
Background: Combination of anti-PD-(L)1 antibody with chemotherapy has shown promising efficacy in advanced/metastatic non-small cell lung cancer (NSCLC). Dynamics of peripheral blood mononuclear cells (PBMC) might have impact on repertore of immune cells further resulting different immune infiltration in tumor microenvironment. Thus, monitoring changes in PBMC during therapy or measuring tumor microenvironment provides the possibility to predict the efficacy of tumor immunotherapy.
Methods: Patients diagnosed with NSCLC (Stage III-IV)were enrolled in this study. Anti-PD-L1 and chemo/radio combination therapy was performed as adjuvant therapy. Tumor samples were obtained prior to adjuvant therapy PBMC samples were obtaind at multiple time points, including prior adjuvant therapy, 3 months after adjuvant therapy, and 3 months after adjuvant therapy. Tumor and PBMC mRNA sequencing were performed by Amoy Diagnostics Co Ltd. (Xiamen, China). Patients who achieved CR/PR/SD and PFS &gt; 6 months were defined as well responders. Pathway enrichment and GSEA analyses were performed by clusterProfiler (version 4.0.5) on GO, KEGG, and from six different gene sets. Correlations between immune cellular signature ES scores and gene expression were estimated using Pearson correlation.
Results: 28 patients were enrolled; mean age was 60.38±7.86 years, 27 (96.4%) patients were male. 21 (75.0%) patients were identified as responder and 7 (25.0%) were non-responder. In the baseline tumor samples, immune infiltration was more extensive in responders compared to non-responders. Cytotoxic lymphocytes, activated CD8+ T cell, and NK cells were significantly enriched in responders. High expression of CCL17 and down regulation of CTSG/PLK1/PRTN3, a signaling axis that inhibits histone H3 hydrolysis and promotes monocyte to macrophage differentiation, was significant in responders. Dynamic monitoring of PBMC before and after treatment showed significant upregulation of immune infiltration-related pathways in responders, including effector cells, NK cells and CD8+ T cells. In the non-responder group, the up-regulated pathways after treatment were mainly enriched in tumor growth rate, EMT, and matrix remodeling. Multi-time point analysis showed that CEACAM5/MKI67 level and tumor proliferation rate in non-responders were higher than those in responders at each time point after treatment.
Conclusion: Baseline tumor transcripton signatures and dynamic changes in PBMC could be applied to develop novel biomarkers for immune-related therapy. Patients with stronger immune infiltration signals in baseline tumor samples and PBMC after treatment had better immune response. The upregulation of proliferation-related signals in PBMC predicts poor immune response.
Citation Format: Jing Hu, Jianguo Zhang, Peng Cheng, Yanhua Chen, Changbin Zhu, Feilin Yi, Conghua Xie. Transcriptome analysis of tissues and peripheral blood revealed potential biomarkers for chemo/radio-immunotherapy in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6428.