2023 World Conference on Lung Cancer (Posters)-P1.21. Upregulation of HLA-I/II and Pro-inflammatory Cells in PBMCs Indicated Efficacy of Neoadjuvant Chemo-immunotherapy in Locally Advanced NSCLC

P1.21. Upregulation of HLA-I/II and Pro-inflammatory Cells in PBMCs Indicated Efficacy of Neoadjuvant Chemo-immunotherapy in Locally Advanced NSCLC - PDF(Slides)

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In this study, researchers aimed to evaluate the immune activation status and treatment response in patients receiving neoadjuvant immunotherapy by analyzing gene expression profiles in peripheral blood mononuclear cells (PBMCs). A total of 43 patients with locally advanced non-small cell lung cancer (NSCLC) were enrolled in the study. PBMCs were collected at different time points during the treatment course and gene expression was analyzed using targeted RNA sequencing. The researchers also used computational models to predict immune cell components and performed single-sample gene set enrichment analysis.<br /><br />The results showed that there was a rapid activation of HLA-I/II expression in PBMCs after one week of immunotherapy administration. The transition of CD8 cells from naïve to cytotoxic T cells during the first two treatment courses suggested the therapeutic efficacy and responsive mechanism of immunotherapy. Cytokines and proinflammatory factors were over-presented in patients who exhibited a positive response to treatment after two treatment courses.<br /><br />The gene expression profiles of PBMCs differed between the responders (MPR group) and non-responders (non-MPR group). The MPR group showed upregulation of the MHC I antigen presentation pathway and CD8 T cell differentiation after the first course of chemo-immunotherapy. In the second course, the antigen presenting process was continuously activated in the MPR group, while it was downregulated in the non-MPR group. After two cycles of chemo-immunotherapy, IFN-γ signatures were over-presented in the MPR group, while a rapid decline of NK cells was observed in the non-MPR group. Additionally, PBMCs from the MPR group exhibited stable expression levels of pro-inflammatory molecules, while expression of these molecules continued to decrease in PBMCs from non-MPR patients.<br /><br />Overall, this study suggests that analyzing gene expression profiles in PBMCs can provide valuable insights into immune activation status and treatment response in patients receiving neoadjuvant immunotherapy for NSCLC. These findings may contribute to the development of liquid biopsy approaches for evaluating immune activation and treatment response in cancer patients.

Asset Subtitle

Hui Kang Xie

Meta Tag

Speaker Hui Kang Xie

Topic Pathology & Biomarkers: Biomarkers for Immuno-oncology

Keywords

immune activation

treatment response

neoadjuvant immunotherapy

gene expression profiles

PBMCs

non-small cell lung cancer

cytotoxic T cells

chemo-immunotherapy

IFN-γ signatures

liquid biopsy