WCLC 2025 - Posters & ePosters-EP.13.41 Expression of PD-L1 and Alternative Immune Checkpoints (ICs) and Their Impact on Outcomes in Small Cell Lung Cancer (SCLC)

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This study investigates the expression of PD-L1 and alternative immune checkpoints (ICs)—including B7-H3, B7x, and B7-H7—in small cell lung cancer (SCLC), exploring their distribution across molecular subtypes and their association with clinical outcomes, particularly overall survival (OS) and time on treatment (TOT) following immunotherapy (IO).<br /><br />Using extensive next-generation sequencing (DNA and whole transcriptome sequencing [WTS]) on 2,187 SCLC samples, PD-L1 expression was assessed by immunohistochemistry (IHC) and WTS. The study stratified SCLC into four transcriptional subtypes—ASCL1 (A), POU2F3 (P), NEUROD1 (N), and Inflamed (I)—and examined IC gene expression patterns by tumor biopsy site (lung, lymph node, bone, brain). Insurance claims data were used to correlate molecular findings with survival outcomes, applying Cox models and log-rank tests for statistical significance.<br /><br />Key findings include a significant positive correlation between PD-L1 expression and improved OS in patients treated with immunotherapy (HR 1.38 by WTS, p=0.003; HR 1.52 by IHC, p=0.001), with low PD-L1 expression or negativity associated with poorer survival. Expression levels of IC genes varied distinctly across SCLC subtypes and biopsy sites, underscoring tumor heterogeneity. Notably, B7-H3 expression was also linked to survival outcomes (OS HR 1.27, p=0.06; TOT HR 1.32, p=0.013), suggesting its relevance in SCLC immune modulation. Immune cell infiltration positively correlated with higher PD-L1 and alternative IC expression.<br /><br />The study highlights that gene expression profiling via WTS offers clinical insight independent from IHC, supporting its utility in personalizing immunotherapy strategies for SCLC. It emphasizes the heterogeneous immune landscape of SCLC, which may influence therapeutic responsiveness. The authors conclude that further investigation into alternative ICs and their biological and clinical roles is warranted to optimize SCLC management and improve patient outcomes.<br /><br />In summary, this work suggests that PD-L1 and other immune checkpoints represent promising biomarkers and potential therapeutic targets in SCLC, with gene expression profiling providing valuable information beyond traditional histological methods.

Asset Subtitle

Mumtu Lalla

Meta Tag

Speaker Mumtu Lalla

Topic Small Cell Lung Cancer and Neuroendocrine Tumors

Keywords

PD-L1 expression

immune checkpoints

small cell lung cancer

molecular subtypes

immunotherapy outcomes

gene expression profiling

B7-H3

tumor heterogeneity

overall survival

immune cell infiltration