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. 2024 Feb 6;14(5):766–785. doi: 10.1158/2159-8290.CD-23-0857

Figure 6.

Figure 6. Multicellular hubs underlie chemoimmunotherapy resistance and response. A, cNMF was performed on epithelial cells at FU2. Shown is the mean usage of each cNMF gene program in the epithelial cells of fast and slow progressing patients. B, Heat map showing pairwise correlation of gene program activities across all patient samples at FU2 using the 90th percentile of patient-level program activity in epithelial, myeloid, T, NK, and stromal cells. Hierarchical clustering was performed to identify clusters of covarying proteins, which have been labeled as Hub1C to 5C. C, Average z-scored usage of all gene programs in each hub split by fast and slow progressing patients. Statistical comparison performed using a two-sample t test with Bonferroni correction. D, Summary schematic of proposed changes to the TME after 1 cycle of chemotherapy and chemoimmunotherapy in fast versus slow progressing patients; in particular, fast progressing patients have induction of metaplasia programs and increased abundance of suppressive M2 macrophages. Slow progressing patients have increased infiltration of CXCL13+ CD8 T cells after chemotherapy, and increased tumor-intrinsic ISG induction and inflammatory M1 macrophage subsets.

Multicellular hubs underlie chemoimmunotherapy resistance and response. A, cNMF was performed on epithelial cells at FU2. Shown is the mean usage of each cNMF gene program in the epithelial cells of fast and slow progressing patients. B, Heat map showing pairwise correlation of gene program activities across all patient samples at FU2 using the 90th percentile of patient-level program activity in epithelial, myeloid, T, NK, and stromal cells. Hierarchical clustering was performed to identify clusters of covarying proteins, which have been labeled as Hub1C to 5C. C, Average z-scored usage of all gene programs in each hub split by fast and slow progressing patients. Statistical comparison performed using a two-sample t test with Bonferroni correction. D, Summary schematic of proposed changes to the TME after 1 cycle of chemotherapy and chemoimmunotherapy in fast versus slow progressing patients; in particular, fast progressing patients have induction of metaplasia programs and increased abundance of suppressive M2 macrophages. Slow progressing patients have increased infiltration of CXCL13+ CD8 T cells after chemotherapy, and increased tumor-intrinsic ISG induction and inflammatory M1 macrophage subsets.