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. 2022 Nov 7;12:877635. doi: 10.3389/fonc.2022.877635

Figure 5.

Figure 5

Increased central memory and cytotoxic T cell frequencies in CRC PDX MSS tumors explanted from HIS-BRGS mice treated with cabozantinib/nivolumab (Ca/N) combination relative to those treated with cobimetinib/atezolizumab (Co/A). Phenotypes of human immune system in LN, spleen (SP) and TILs (CU-CRC307P) from HIS-BRGS mice treated with nothing (V), atezolizumab (A), cobimetinib (Co), combination Co/A or Ca/N: frequencies and/or numbers of (A) hCD45+ (Top row) and human T cells (CD3+, bottom row), (B) T cell populations (CD4+ top, CD8+ bottom) in the CRC307P TILS: activated HLA-DR+ (left panel), effector memory (CCR7-, CD45RO+, left middle panel), central memory (CCR7+, CD45RO+, right middle panel) and exhausted TIM-3+ (right panel); (C) Cytotoxic T cells (CD4+ top, CD8+ bottom) expressing Granzyme B (left panels) ex vivo or TNFα (left middle panels), IFNγ (right middle panels) or both TNFαIFNγ (right panels) following overnight cell stim and 4 hour Golgi block; (D) T regs (FoxP3+, CD25+) in LN (upper) and tumor (bottom); and (E) expression (MFI) of MHC class I (HLA-ABC, left), class II (HLA-DR, middle) and PD-L1 (right) on CRC307P EpCAM+ tumor cells. P-values indicate ANOVA multiple comparisons with Welch’s correction: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 or as indicated by number.