High-dimensional in situ proteomics imaging to assess γδ T cells in spatial biology

This study presents a high-dimensional immunohistochemistry approach to assess human gamma delta T cell subsets in their native tissue microenvironments at spatial resolution, a hitherto unmet scientific goal due to the lack of established antibodies and required technology. We report an integrated approach based on multiplexed imaging and bioinformatic analysis to identify gamma delta T cells, characterize their phenotypes, and analyze the composition of their microenvironment. Twenty-eight gamma delta T cell microenvironments were identified in tissue samples from fresh frozen human colon and colorectal cancer where interaction partners of the immune system, but also cancer cells were discovered in close proximity to gamma delta T cells, visualizing their potential contributions to cancer immunosurveillance. While this proof-of-principle study demonstrates the potential of this cutting-edge technology to assess gamma delta T cell heterogeneity and to investigate their microenvironment, future comprehensive studies are warranted to associate phenotypes and microenvironment profiles with features such as relevant clinical characteristics.