2023 World Conference on Lung Cancer (Posters)-P2.05. Immune Suppressive Microenvironment in Liver Metastases Contributes to Organ-Specific Response of Immunotherapy

P2.05. Immune Suppressive Microenvironment in Liver Metastases Contributes to Organ-Specific Response of Immunotherapy - PDF(Slides)

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Liver metastases (LM) in non-small cell lung cancer (NSCLC) patients can diminish the effectiveness of immunotherapy. This study aimed to determine if there is a difference in tumor response to immunotherapy between pulmonary lesions (PL) and LM in NSCLC. The researchers conducted a clinical cohort study involving NSCLC patients with LM who were receiving immunotherapy. They evaluated the organ-specific tumor response of PL and LM. They also performed multi-omics analysis to explore potential mechanisms.<br /><br />The results showed that the disease control rate of LM was lower than that of PL. One-third of patients had mixed responses, with the majority showing an increase in LM. Genomic analysis revealed similar somatic mutations, tumor mutational burden, and neoantigen numbers between PL and LM. However, immune activation-related genes were downregulated in LM. Additionally, the antigen presenting and NK cell-mediated cytotoxicity pathways were more enriched in PL. The CIBERSORT approach showed that there were more CD8T cells infiltrating PL compared to LM. Furthermore, multiplex immunohistochemistry confirmed that there were significantly lower fractions of CD8 cells and CD56dim cells in LM compared to PL.<br /><br />In conclusion, LM exhibits an inferior organ-specific tumor response to immunotherapy compared to PL in NSCLC patients. Although PL and LM show limited heterogeneity in the genomic landscape, the tumor microenvironment in LM presents lower levels of immune activation and infiltration. These findings suggest the need for the development of precise immunotherapy strategies for NSCLC patients with LM.

Asset Subtitle

Jia-Yi Deng

Meta Tag

Speaker Jia-Yi Deng

Topic Metastatic NSCLC: Immunotherapy - Biomarker

Keywords

Liver metastases

NSCLC

immunotherapy

tumor response

pulmonary lesions

genomic analysis

immune activation

CD8T cells

tumor microenvironment

precise immunotherapy strategies