WCLC 2025 - Posters & ePosters-P1.11.70 Immune Cell Infiltration and Spatial Associations in the Tumor Microenvironment Following Dual ICI or ICI-Chemotherapy

Pdf Summary

This study investigates how different lung cancer treatments—dual immune checkpoint inhibition (dual-ICI, combining anti-PD-L1 and anti-CTLA4) and immune checkpoint inhibition plus chemotherapy (ICI-chemo)—affect tumor microenvironment (TME) immune composition and cell spatial interactions. Using imaging mass cytometry (IMC), the researchers profiled immune and epithelial cell types and their spatial relationships in tumor samples collected before and after treatment.<br /><br />Key findings include increased infiltration of neutrophils, natural killer (NK) cells, and dendritic cells in post-treatment samples from both groups. Regulatory T cells (Tregs) were significantly elevated only in dual-ICI post-treatment samples, alongside persistent epithelial cells that exhibited spatial avoidance of immune and stromal cells. In contrast, ICI-chemo treatment drove greater overall immune cell infiltration and promoted active engagement between epithelial, immune, and stromal cells.<br /><br />Spatial analyses identified eight distinct cell neighborhood structures post-treatment. The dual-ICI group maintained complex immune hubs comprising B cells, dendritic cells, CD4 T cells, and myeloid cells, whereas in the ICI-chemo group, these neighborhoods shifted, with fewer T cells and myeloid cells present. Additionally, cellular interaction patterns diverged: dual-ICI samples showed active immune-stromal interactions and epithelial cell avoidance, while ICI-chemo samples exhibited immune cell avoidance and epithelial-immune contact.<br /><br />Importantly, the formation of B cell–T cell–dendritic cell triads increased significantly after treatment and correlated with treatment response. These triads were not predictive pre-treatment but were more frequent post-treatment in responders than non-responders, suggesting their potential role as biomarkers of effective immune remodeling and clinical benefit.<br /><br />In summary, dual-ICI and ICI-chemo therapies evoke distinct immune remodeling patterns in lung tumors. Dual-ICI preserves complex multicellular immune neighborhoods and regulatory T cells, whereas ICI-chemo promotes broader immune infiltration and epithelial-immune interactions. The enrichment of immune triads after treatment signals favorable response, providing insight into TME dynamics that could guide personalized immunotherapy strategies.

Asset Subtitle

Natalie Vokes

Meta Tag

Speaker Natalie Vokes

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

lung cancer

immune checkpoint inhibition

dual-ICI

ICI-chemo

tumor microenvironment

imaging mass cytometry

immune cell infiltration

cell spatial interactions

B cell-T cell-dendritic cell triads

immunotherapy response biomarkers