2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.06E.01 Preexisting CD153+CD4+ T Cells Cause Lung Specific Toxicity via Type 3 Immunity without Kidnapping Efficacy in Immunotherapy

EP.06E.01 Preexisting CD153+CD4+ T Cells Cause Lung Specific Toxicity via Type 3 Immunity without Kidnapping Efficacy in Immunotherapy

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The document highlights a study on CD153 CD4 T cells, suggesting they could be reliable predictors for lung-specific toxicity during immune checkpoint blockade (ICB) immunotherapy, without affecting the therapy's efficacy. Immune-related pneumonitis (IRP), a concerning adverse effect of ICB, can lead to treatment discontinuation or even fatal outcomes. However, the mechanisms underlying IRP remain poorly understood.<br /><br />Researchers performed single-cell RNA sequencing (scRNA-seq) to analyze immune cells from blood samples of cancer patients before treatment and during grade 2-3 IRP. They aimed to identify candidate genes associated with IRP and tested their findings across various data sets, including real-world pharmacovigilance data, the Cancer Genome Atlas (TCGA), and flow cytometry.<br /><br />The study found that increased expression of CD153, a protein primarily present on CD4 T cells, is linked with IRP, specifically affecting the lungs but not other organs. This correlation was also supported by the presence of CD30, the ligand for CD153, which showed similar patterns. Notably, the presence of these markers did not compromise the effectiveness of ICB therapy, as evaluated across three independent cohorts.<br /><br />Furthermore, the study identified a pro-inflammatory subgroup of CD4 T cells, characterized by high levels of CD153 and type 3 immunity markers, which are generally associated with autoinflammatory conditions. The blockade of CD153 or type 3 immunity pathways might therefore provide a strategy to reduce lung-specific toxicity while maintaining the therapeutic benefits of ICB. <br /><br />This research advances understanding of ICB-related irAEs and suggests potential interventions to mitigate lung toxicity without compromising cancer treatment efficacy.

Asset Subtitle

Zi-Xuan Rong

Meta Tag

Speaker Zi-Xuan Rong

Topic Pathology and Biomarkers

Keywords

CD153 CD4 T cells

immune checkpoint blockade

lung-specific toxicity

immune-related pneumonitis

single-cell RNA sequencing

candidate genes

pro-inflammatory CD4 T cells

type 3 immunity

autoinflammatory conditions

cancer treatment efficacy