WCLC 2025 - Posters & ePosters-P3.13.06 Comprehensive Assessment of the Tumor Microenvironment of Resected Small Cell Lung Cancer

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This study presents a comprehensive assessment of the tumor immune microenvironment (TIME) in resected small cell lung cancer (SCLC), which accounts for 15% of lung cancers and has a poor 5-year survival rate of 5%. Although four transcription factor-based molecular subtypes of SCLC have been identified—ASCL1, NeuroD1, POU2F3, and an "inflamed" group—little is known about how these subtypes relate to the TIME or prognosis. The study aimed to characterize TIME across these molecular subtypes while addressing intratumoral heterogeneity using tissue microarrays (TMAs) from 56 resected SCLC patients.<br /><br />Molecular subtyping was performed by immunohistochemistry (IHC) for ASCL1, NeuroD1, and POU2F3. TIME profiling was conducted with CyTOF (cytometry by time-of-flight) single-cell analysis using 36 markers on approximately 500,000 cells across multiple tumor cores per patient. Associations between molecular subtypes, immune cell types, cellular neighborhoods, clinical-pathological features, and prognosis were examined.<br /><br />Results showed few significant differences in TIME composition between molecular subtypes. Notably, NeuroD1 tumors had higher levels of classical monocytes, and POU2F3 tumors exhibited increased vascularization compared to other subtypes. Most patients’ multiple tumor cores clustered similarly, supporting some intratumoral homogeneity of immune features, though some heterogeneity existed. Importantly, no significant differences in overall survival were found across the subtypes in this resected cohort.<br /><br />Overall, transcription factor-based molecular subtyping was not strongly linked to distinct TIME characteristics or survival outcomes. IHC subtyping alone cannot reliably predict TIME composition, highlighting the complexity and heterogeneity of SCLC immune landscapes. Further research is ongoing to define patient groups with differing TIME profiles that may guide biomarker and therapeutic developments. This study underscores the challenges of translating molecular subtyping into prognostic or predictive clinical tools in SCLC.

Asset Subtitle

Andréanne Gagné

Meta Tag

Speaker Andréanne Gagné

Topic Small Cell Lung Cancer and Neuroendocrine Tumors

Keywords

small cell lung cancer

tumor immune microenvironment

molecular subtypes

ASCL1

NeuroD1

POU2F3

CyTOF

immunohistochemistry

intratumoral heterogeneity

prognosis