CCL20 Released by Drug-Tolerant Persisters Impairs Immunotherapy in EGFR-Mutated Lung Adenocarcinoma

Drug-tolerant persisters (DTPs), a subpopulation of cancer cells that can survive initial therapy, contribute to this resistance by releasing CCL20, a chemokine that fosters tumor immune privilege. This preclinical study aims to explore the role of CCL20 in modulating TIME and its impact on ICI efficacy in EGFR-mutated LUAD.

We utilized a humanized mouse model engrafted with EGFR-mutated NCI-H1975 LUAD cells and human peripheral blood mononuclear cells (PBMCs) to mimic a human immune system. Mice were treated with anti-PD-1, anti-CCL20, or a combination of both. Xenograft growth was monitored, and resected xenograft were analyzed using single-cell RNA sequencing (scRNA-seq) and multiplex immunofluorescence microscopy to assess changes in tumor cell transcriptional profiles and immune cell infiltration including.