2023 Targeted Therapies of Lung Cancer Meeting (Poster)-P1.29. The LAG-3/FGL1 Axis is a Dominant Immune Evasion Pathway in NSCLC Modulated by Hypoxia

P1.29. The LAG-3/FGL1 Axis is a Dominant Immune Evasion Pathway in NSCLC Modulated by Hypoxia

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The LAG-3/FGL1 axis is an immune evasion pathway that plays a role in non-small cell lung cancer (NSCLC), particularly under hypoxic conditions. LAG-3 is an inhibitory receptor expressed on activated T-cells, while Fibrinogen-like 1 (FGL1) mediates T-cell suppression. In this study, researchers used Imaging Mass Cytometry to map the LAG-3/FGL1 pathway and characterize the immune contexture and hypoxia in NSCLC samples from two patient cohorts. They found that FGL1 protein was expressed in about 18% of NSCLC samples, and its expression was associated with dysfunctional tumor-infiltrating lymphocytes (TILs) and tumor-cell hypoxia. NSCLC tumors with high FGL1 expression had increased levels of CD8 TILs with an activated/dysfunctional phenotype. They also found that elevated FGL1 expression predicted shorter survival in NSCLC patients treated with PD-1 axis blockers. Hypoxia was found to induce FGL1 expression in tumor cells and alter T-cell function in in vitro experiments. These findings suggest that the LAG-3/FGL1 axis is a dominant immune evasion pathway in a subset of NSCLC tumors and is modulated by tumor microenvironment hypoxia. Blocking the LAG-3/FGL1 pathway could potentially enhance anti-tumor responses in NSCLC. Further research is needed to explore therapeutic strategies targeting this pathway.

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Maria Villalba Esparza, Yale University, United States

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Speaker Maria Villalba Esparza, Yale University, United States

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Keywords

LAG-3/FGL1 axis

immune evasion pathway

NSCLC

hypoxic conditions

T-cells

FGL1 protein

tumor-infiltrating lymphocytes

CD8 TILs

PD-1 axis blockers

tumor microenvironment