# Multi-omics profiling reveals microenvironmental remodeling as a key driver of house dust mite-induced lung cancer progression

## TL;DR

Chronic exposure to house dust mites promotes lung cancer by altering the lung's immune environment, not through DNA mutations.

## Contribution

The study identifies IL-17A as a key driver of HDM-induced lung tumor progression through immune remodeling.

## Key findings

- HDM exposure accelerates tumor growth without changing mutation rates.
- HDM suppresses T cell responses and promotes myeloid cell dominance in tumors.
- IL-17A is essential for HDM-driven tumor promotion, unlike IL-1β.

## Abstract

•Chronic house dust mite (HDM) exposure accelerates lung tumor growth through non-mutagenic, immune-mediated mechanisms.•HDM activates pro-inflammatory and immune programs in normal lung tissue but suppresses antitumor T cell responses in tumors.•Multi-omics profiling reveals epigenetic silencing of immune genes and a myeloid-enriched, lymphoid-deficient tumor microenvironment.•HDM-driven tumor promotion depends on IL-17A but not IL-1β, establishing IL-17A as a central driver of lung tumor promotion.

Chronic house dust mite (HDM) exposure accelerates lung tumor growth through non-mutagenic, immune-mediated mechanisms.

HDM activates pro-inflammatory and immune programs in normal lung tissue but suppresses antitumor T cell responses in tumors.

Multi-omics profiling reveals epigenetic silencing of immune genes and a myeloid-enriched, lymphoid-deficient tumor microenvironment.

HDM-driven tumor promotion depends on IL-17A but not IL-1β, establishing IL-17A as a central driver of lung tumor promotion.

Chronic exposure to the common aeroallergen house dust mite (HDM) induces lung inflammation and DNA damage, but its impact on lung cancer development remains largely unexplored. Using whole-genome sequencing, RNA-seq, and DNA methylation profiling, we assessed HDM effects in lung epithelial cell lines and a mouse orthotopic lung cancer model. HDM accelerated tumor growth without altering mutational burden. Transcriptomic and epigenetic analyses revealed tissue-specific effects: in normal lung, HDM enhanced pro-inflammatory and immune activation programs, whereas in tumors it suppressed T cell responses, antigen presentation, and chemokine signaling. Immune deconvolution showed a shift toward myeloid enrichment and lymphoid suppression, with reduced cytotoxic T and NK signatures. Notably, HDM-driven tumor promotion was abolished in Il17a−/− but not Il1b−/− mice, identifying IL-17A as a critical mediator. These findings demonstrate that chronic aeroallergen exposure reshapes the lung microenvironment to promote immune suppression and accelerate lung cancer progression.

Image, graphical abstract