2024 World Conference on Lung Cancer (WCLC) - Posters-P3.06F.05 Spatial Profiling of the Tumor Microenvironment of SMARCA4-Mutant NSCLCs Using Whole-Slide Multiplex Fluorescence Imaging

P3.06F.05 Spatial Profiling of the Tumor Microenvironment of SMARCA4-Mutant NSCLCs Using Whole-Slide Multiplex Fluorescence Imaging

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The study conducted spatial profiling of the tumor immune microenvironment (TME) in SMARCA4-mutant non-small cell lung cancers (NSCLCs) using whole-slide multiplex fluorescence imaging. SMARCA4 mutations, prevalent in 10% of NSCLCs, are linked with poor prognosis, primarily affecting cases with adenocarcinomas and a smoking history. These mutations show resistance to immune checkpoint inhibitors (ICIs), although the reasons are unclear, potentially relating to high tumor mutational burden (TMB), varied PD-L1 tumor proportion scores (TPS), and other mutations such as STK11. <br /><br />The researchers hypothesized that the ICI resistance might stem from impaired immune infiltration, and analyzed samples through whole-slide cyclic immunofluorescence (CyCIF) with a 60-plex panel. The cohort included 38 patients, predominantly with SMARCA4-mutant NSCLCs. The study found that these tumors had high TMB and low PD-L1 expression, with reduced expression of markers like cytokeratin and TTF1, indicating a high proliferation rate. <br /><br />While SMARCA4-mutant NSCLCs did not universally show immune-cold profiles, there was a general trend of reduced CD8, CD4, and CD20 immune cell presence. Tertiary lymphoid structures (TLS) were less frequent in SMARCA4-mutant tumors, and these findings persisted irrespective of the presence of additional STK11 mutations. <br /><br />Conclusively, the study suggests that while SMARCA4 mutations are associated with certain immune and proliferation characteristics, the tumors are not entirely devoid of immune presence. Future research will explore outlier cases, perform neighborhood analyses, increase sample sizes, and investigate the influence of sample locations and additional co-mutations.

Asset Subtitle

Andréanne Gagné

Meta Tag

Speaker Andréanne Gagné

Topic Pathology & Biomarkers

Keywords

SMARCA4-mutant

non-small cell lung cancer

tumor immune microenvironment

immune checkpoint inhibitors

tumor mutational burden

PD-L1 expression

cyclic immunofluorescence

immune infiltration

tertiary lymphoid structures

STK11 mutations