2023 World Conference on Lung Cancer (Posters)-P1.24. Clinicopathological Characteristics of Pulmonary Squamous Cell Carcinoma with KDM5D Copy Number Loss

P1.24. Clinicopathological Characteristics of Pulmonary Squamous Cell Carcinoma with KDM5D Copy Number Loss - PDF(Slides)

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Approximately 40% of patients with lung squamous cell carcinoma (SCC) exhibit copy number loss of the KDM5D gene. This genetic alteration is associated with late-stage disease and high stromal content. Furthermore, SCCs with KDM5D copy number loss are characterized by a lack of infiltrating CD8/T-bet T cells, making them unlikely to respond to immunotherapy. Therefore, these patients may be good candidates for targeted therapies involving ATR inhibitors.<br /><br />The study evaluated 173 SCC samples from male patients and used fluorescence in situ hybridization to detect KDM5D copy number loss. It was found that 43% of the patients had this genetic alteration. Gene expression profiling further revealed that upregulated genes in tumors with KDM5D copy number loss are associated with the cell cycle, while downregulated genes are associated with the immune response.<br /><br />Clinically, SCCs with KDM5D copy number loss were associated with late-stage disease and high stromal content. Multiplexed fluorescent immunohistochemistry showed that the number of tumor-infiltrating CD8/T-bet T cells was smaller in SCCs with KDM5D copy number loss compared to wild-type tumors.<br /><br />The findings suggest that patients with SCC and KDM5D copy number loss may have "cold tumors" that do not respond well to immunotherapy. However, they may benefit from ATR inhibitor treatment. Overall, this study highlights the prevalence and clinical significance of KDM5D copy number loss in SCC and its potential as a predictive biomarker for targeted therapies.

Asset Subtitle

Takuo Hayashi

Meta Tag

Speaker Takuo Hayashi

Topic Pathology & Biomarkers: Prognostic Biomarkers

Keywords

lung squamous cell carcinoma

copy number loss

KDM5D gene

late-stage disease

high stromal content

CD8/T-bet T cells

immunotherapy

targeted therapies

ATR inhibitors

gene expression profiling