PT - JOURNAL ARTICLE AU - Mark Sorin AU - Elham Karimi AU - Morteza Rezanejad AU - Miranda W Yu AU - Lysanne Desharnais AU - Sheri A C McDowell AU - Samuel Doré AU - Azadeh Arabzadeh AU - Valerie Breton AU - Benoit Fiset AU - Yuhong Wei AU - Roni Rayes AU - Michele Orain AU - Francois Coulombe AU - Venkata S K Manem AU - Andreanne Gagne AU - Daniela F Quail AU - Philippe Joubert AU - Jonathan D Spicer AU - Logan A Walsh TI - Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunity AID - 10.1136/jitc-2022-005545 DP - 2023 Feb 01 TA - Journal for ImmunoTherapy of Cancer PG - e005545 VI - 11 IP - 2 4099 - http://jitc.bmj.com/content/11/2/e005545.short 4100 - http://jitc.bmj.com/content/11/2/e005545.full SO - J Immunother Cancer2023 Feb 01; 11 AB - Background Immunotherapy has revolutionized clinical outcomes for patients suffering from lung cancer, yet relatively few patients sustain long-term durable responses. Recent studies have demonstrated that the tumor immune microenvironment fosters tumorous heterogeneity and mediates both disease progression and response to immune checkpoint inhibitors (ICI). As such, there is an unmet need to elucidate the spatially defined single-cell landscape of the lung cancer microenvironment to understand the mechanisms of disease progression and identify biomarkers of response to ICI.Methods Here, in this study, we applied imaging mass cytometry to characterize the tumor and immunological landscape of immunotherapy response in non-small cell lung cancer by describing activated cell states, cellular interactions and neighborhoods associated with improved efficacy. We functionally validated our findings using preclinical mouse models of cancer treated with anti-programmed cell death protein-1 (PD-1) immune checkpoint blockade.Results We resolved 114,524 single cells in 27 patients treated with ICI, enabling spatial resolution of immune lineages and activation states with distinct clinical outcomes. We demonstrated that CXCL13 expression is associated with ICI efficacy in patients, and that recombinant CXCL13 potentiates anti-PD-1 response in vivo in association with increased antigen experienced T cell subsets and reduced CCR2+ monocytes.Discussion Our results provide a high-resolution molecular resource and illustrate the importance of major immune lineages as well as their functional substates in understanding the role of the tumor immune microenvironment in response to ICIs.Data are available upon reasonable request.