Tissue environment

Immune cells do not exist in isolation. Instead, they are constantly communicating with neighboring cells, reacting to systemic cytokines, and receiving signals from vessels, neurons, and other surrounding structures. We have leveraged technological advances in spatial transcriptomics and spatial proteomics to explore how immune cells react to environmental cues and spatially reorganize in the setting of disease. In a murine model, we have highlighted how alveolar macrophages (AMs) interact with cancer cells during early tumor seeding but become spatially excluded as the tumor grows, suggesting that AMs directly support tumor seeding. Using spatial transcriptomics data from patients, we identified niches of mature DCs co-localized with CXCL13+ Tfh and effector CD8+ T cells that were associated with improved immunotherapy response. These studies underscore the importance of collecting datasets from both human and mouse studies and validate our findings in cross-species comparisons. More recently, we have amassed large spatial cohorts of human lesions across lung, liver, and colorectal cancers using a variety of techniques including 10x Visium, Xenium, Vizgen MERSCOPE, and cyclic immunofluorescence. We also work in close collaboration with the Brown and Gnjatic laboratories at Mount Sinai, both of whom have developed novel in vivo approaches for protein imaging and perturbation screening. With many new techniques on the horizon, we are excited to adapt platforms into our laboratory which may provide insight into how tissues become spatially dysregulated during disease progression. 

Key reference

• Pipeline for multiplexed image analysis: Buckup … Merad, Gnjatic, Nature Biomedical Engineering, 2025.

• Spatial screening in lung cancer: Dhainaut … Merad, Brown, Cell 2022.

• Distinct AM positioning during tumor growth: Casanova-Acebes … Merad, Nature 2021.