Abstract
Multiplexed immune profiling of the tumor microenvironment (TME) in cancer has improved our understanding of cancer immunology, but complex spatial analyses of tumor immune interactions are lacking. Here we used imaging mass cytometry (IMC) to characterize the immunophenotypes and the spatial architecture in the TME of 33 cases of DLBCL. We develop the M-score, for identifying complex cellular phenotypes, and use this to identify a CCR4+Tim3+PDL1+ tumor phenotype that predicts outcomes better than the lymphoma international prognostic index (IPI). To characterize spatial interaction in the TME, we constructed spatial meta-clusters based on distances from CD8 T cells to other cells in the microenvironment. These clusters corresponded to micro-regions of immuno-suppression or immuno-activation, whose relative abundance correlated with clinical responses to chemotherapy. Finally, the CD8 spatial network alone could predict overall survival in lymphoma and point to a broader application of complex spatial analysis to gain functional insights into cancer immunology.
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