Revolutionary SEPARATE-Seq Technology Maps Lung Cancer Immune Microenvironment to Drive Targeted Immunotherapy Success

VIB-VUB researchers unveil SEPARATE-Seq, a new tool to track immune cells inside lung tumors, bridging the gap between mouse models and patient treatment.

By: AXL Media

Published: Apr 27, 2026, 6:05 AM EDT

Source: Information for this report was sourced from EurekAlert!

Building a More Accurate Mirror of Patient Biology

Lung cancer remains the primary driver of cancer-related deaths globally, yet preclinical research has historically relied on subcutaneous models that fail to replicate the lung's specific environment. Prof. Damya Laoui and her team at the VIB-VUB Center for Inflammation Research have addressed this gap by developing an orthotopic lung adenocarcinoma model where tumors grow directly within the lung. This approach allows researchers to study tumor nodules in their natural anatomical context, mirroring the clinical handling of patient samples. By placing the malignancy in its native environment, the team successfully captured immune dynamics that are absent when cancer is studied under the skin.

Precision Tracking with SEPARATE-Seq Innovation

A critical barrier in cancer research has been the inability to differentiate between immune cells actively fighting a tumor and those merely circulating in nearby blood vessels. To solve this, the researchers introduced SEPARATE-Seq, a methodology that labels immune cells in the blood to partition them from those embedded in tissue. According to Laoui, the signals an immune cell receives while inside a blood vessel differ fundamentally from those it encounters within a tumor. This distinction is vital for understanding cell behavior at single-cell resolution, as it prevents researchers from drawing misleading conclusions based on cells that are only "passing through" the site of the disease.

The Spatial Architecture of Tumor Defense

Combining SEPARATE-Seq with spatial transcriptomics allowed the team to map the precise coordinates of immune activity. Their analysis revealed highly organized patterns, such as a distinct ring of lipid-associated macrophages at the tumor's edge and specific "hubs" of interferon-stimulated cells within the tumor core. They also observed the infiltration of hypoxic neutrophils and a significant shift in natural killer (NK) cells toward a dysfunctional, immature state upon entering the tumor. These spatial insights highlight how the tumor microenvironment physically and chemically reorganizes immune function to create niches that can either promote or hinder cancer growth.