Using multiomics analysis to examine prognostic biomarkers for patients with squamous cell lung carcinoma treated with neoadjuvant therapy of camrelizumab combined with Apatinib.

Abstract

e20563 Background: Immune checkpoint inhibitor (ICI) combined with targeted therapy as a neoadjuvant therapy has been applied to the treatment of squamous cell lung carcinoma (SCLC). However, biomarkers to predict the response are unclear. Methods: 26 SCLC patients treated with neoadjuvant therapy of camrelizumab combined with apatinib were enrolled. Pretreatment samples of these patients were performed with whole-exome sequencing, RNA sequencing, TCR sequencing and IHC of PD-L1 expression. Peripheral blood at different timepoints were collected and analyzed with ctDNA sequencing. Results: At baseline, tumor mutation burden was found to be associated with clinical benefit. For patients with HLA intact, tumor neoantigen burden are significantly increased in the benefited group compared with non-benefited group. Transcriptome analysis revealed that regulatory T cells were significant higher in non-benefited group. In addition, diversity of dominate T-cell receptor repertoire was found to be associated with clinical benefit. Post-treatment, the levels of ctDNA decreased in the benefited group. Conclusions: In this study, we comprehensively analyzed the genomic, tumor microenvironment and serum biomarkers in SCLC patients treated with ICI combined with targeted therapy, and found that TMB, regulatory T cells and change of ctDNA levels were associated with the clinical benefit. In addition, the combination of HLA status and TNB could further distinguish responders.