WCLC 2025 - Posters & ePosters-EP.03.13 LIF Is Associated With Poor Prognosis and Participates in Lung Cancer Growth and Implantation in Preclinical Models of NSCLC

EP.03.13 LIF Is Associated With Poor Prognosis and Participates in Lung Cancer Growth and Implantation in Preclinical Models of NSCLC

Back to course

Pdf Summary

This study by Muñoz-Pinedo et al. investigates the role of Leukemia Inhibitory Factor (LIF), a cytokine implicated in cancer progression, in non-small cell lung cancer (NSCLC). LIF is known to promote tumorigenic processes such as stemness maintenance, immune suppression, and cachexia, and its expression is driven by oncogenic pathways like KRAS.<br /><br />Using data from The Cancer Genome Atlas (TCGA), the researchers found that high LIF expression correlates with poorer overall survival in lung squamous cell carcinoma (LUSC) and shows a similar trend in lung adenocarcinoma (LUAD). In multiple NSCLC cell lines and a murine Lewis Lung Carcinoma (LLC) model, LIF expression and secretion were heterogeneous but increased significantly under stress conditions like glucose deprivation and hypoxia, common in the tumor microenvironment.<br /><br />CRISPR-mediated deletion of LIF in LLC cells reduced tumor growth when injected subcutaneously into mice and impaired lung tumor implantation in an orthotopic tail vein injection model. Tumors lacking LIF exhibited less innate immune infiltration (neutrophils, macrophages) and pro-inflammatory cytokines (IL-6, IL-1α), but showed increased markers indicative of enhanced antitumor immune responses, including interferon gamma, natural killer (NK) cells, and CD8+ T cells.<br /><br />Overall, this work suggests that LIF supports NSCLC progression by promoting tumor growth, implantation, and immune suppression. The findings highlight LIF as a potential therapeutic target to inhibit tumor advancement and improve immune-mediated cancer clearance in NSCLC. Ongoing clinical trials with drugs targeting LIF or its receptor may offer promising treatment avenues.

Asset Subtitle

Cristina Muñoz-Pinedo

Meta Tag

Speaker Cristina Muñoz-Pinedo

Topic Tumor Biology – Translational Biology

Keywords

Leukemia Inhibitory Factor

LIF

non-small cell lung cancer

NSCLC

tumor microenvironment

immune suppression

KRAS pathway

CRISPR deletion

tumor growth

immune response