Fig. 3

Increased radio-resistance of T cells within tumors and non-lymphoid solid organs compared with circulating T cells and T cells from lymphoid organs. a EYFP⁺ T cell reporter mice bearing established MC38 tumors received different doses of WBI, as indicated. Twenty-four hours later, survival of T cells in tumors vs. circulation was determined by flow cytometry (gating in Supplementary Fig. 5). The tumor/blood slopes were significantly different (P = 0.02) by linear regression analysis. b Percentage of CD8⁺ cells among total tumor and blood T cells from the experiment shown in a. % CD8⁺ cells in blood was significantly lower after all WBI doses tested compared to unirradiated mice (P = 0.01 at 1 Gy, <0.001 for the rest, unpaired t-test). In tumors, differences were not significant or % CD8⁺ T cells was higher in irradiated compared to unirradiated mice (P = 0.03 at the 5 Gy dose). Data in a and b were pooled from three independent experiments comparing tumor and blood and one additional experiment with data only from blood. In a, each dot represents an individual mouse whereas b shows average and SD. c–f C57BL/6 mice bearing established (3 weeks) MC38 tumors were treated with 8 Gy WBI (IR) or left untreated (control). Twenty-four hours later, absolute numbers of parenchymal (i.v. antibody-negative) CD8⁺ T cells per gram were determined for the organs and tissues indicated, and fold decrease was calculated in each irradiated mouse and tissue relative to the average number of T cells per gram of tissue in unirradiated mice in the same experiment. Data are pooled from two independent experiments, N = 6 total mice per organ and condition. c shows averages, P values by ratio t-test. Exact P values in Supplementary Table 1. d Average fold decrease in parenchymal CD8⁺ T cells was plotted against the %T_RM in each non-lymphoid solid organ and analyzed by linear regression. e Percent of cells with T_RM phenotype (CD103⁺CD69⁺ for IEL, tumor, and CD69⁺LFA1⁺ for liver) in each organ in mice that received or not IR (average and SD, P values by unpaired t-test). f Effect of IR on T_RM vs. non-T_RM CD8⁺ cells (ratio-paired t-test). n.s., non-significant; ***P ≤ 0.001; ****P ≤ 0.0001