Tumor-immune partitioning and clustering algorithm for identifying tumor-immune cell spatial interaction signatures within the tumor microenvironment
Fig 8
Using TIPC to discern spatial patterns of immune activity in an HCC cohort and their correlation with patient treatment response.
(a) Responders (Rs) exhibited a unique spatial pattern of CXCL9+/CXCR3+ CD68+ macrophages: a uniform distribution of CXCL9+CD68+ cells within tumor regions, along with the co-existence of CXCL9+CD68+ and CXCR3+CD68+ cells, identified as TIPC cluster 1, where CXCR3+CD68+ cells replaced stromal cells in the TIPC analysis. (b) Patients enriched with tumor areas deficient in CXCL9+CD68+ consistently correlate with adverse outcomes, identified as TIPC cluster 2. Additionally, Rs exhibited concurrent enrichment of CXCL9+CD68+ in both tumors and CD8+ regions, where CD8+ T cells replaced stromal cells in the TIPC analysis. Both sets of TIPC subtypes were obtained at the optimal subregion size of 30 µm and input number of clusters of 2, determined based on the most significant p values. Tumor cells were determined as those no expressing CD8, CD68, and CD45 expression.