Tumor-immune partitioning and clustering algorithm for identifying tumor-immune cell spatial interaction signatures within the tumor microenvironment
Fig 3
Characterization of CD3+ T-cell spatial distribution in the CRC tumor microenvironment using TIPC.
Using the optimal subregion size of 35 µm and input cluster number of 9 (which was jointly determined using (a) the consensus cumulative distribution function (CDF) delta plot (k ≥ 4) and (b) tracking plot (k = 9), see S2 Fig for details), the resulting TIPC tumor subtypes and their spatial patterns are represented in (c) a heat-map with corresponding CD3+ T-cell density; subtypes comprising <30 tumors were excluded. (d) Representative cases with similar CD3+ T-cell densities (all within the 3rd quartile) were selected from each of the six main TIPC subtype clusters to illustrate the distinct spatial organization of CD3+ T cells in CRC. From top to bottom, the panels show TIPC subregion categories, cell locations, multiplexed immunofluorescence-based histology, and H&E-stained histology of adjacent slides. TIPC spatial parameter values are depicted on a linear scale showing ordered from left to right: tumor-only, I:T low, I:T high, stroma-only, I:S low, I:S high subregion categories. Abbreviations: I:T = immune-to-tumor, I:S = immune-to-stroma, CSR = cold, stroma-rich, CTR = cold, tumor-rich, HTCC = hot, tumor-centric clustering, HD = hot and disperse, HSCC = hot, stroma-centric clustering, HC = hot and clustered, and O = outliers.