Fig. 8: DC-like reprogramming promotes TIS-preferential T-cell-governed anti-lymphoma immunosurveillance.

a Mouse immunization by inoculating therapy-induced senescent (TIS) or treatment-naïve (UT) control;bcl2 lymphomas twice. Primed spleen pan-T-cells isolated two weeks later. b Viability of control;bcl2;sh_ctrl lymphomas 6-day-exposed to adriamycin (ADR) or left untreated (Target; n = 8 lymphomas), then co-cultured for 72-hr with T-cells (Effector) from a (T_TIS or T_UT) or from wild-type mice (T_naïve). c Activation of CD3⁺CD8⁺ T-cells as mean percentage CD69⁺ ± SEM after co-cultures from b. d Viability of individual UT vs. ADR-exposed control;bcl2 lymphomas (n = 5 each) 48-hr co-cultured with CD4⁺ and CD8⁺ T_TIS subsets. e As in b, but for Spi1-depleted lymphomas (sh_Spi). Viabilities normalized to matched conditions of paired sh_ctrl lymphomas (b). f As in c, but showing the difference in CD69⁺CD8⁺ T-cells between matched sh_Spi1 and sh_ctrl specimens. g Analogous to b and e, but assessing PD-L1 blockade effect (αPD-L1) on lymphoma viability (legend on the right) post co-culture with T_TIS or T_UT. Viabilities normalized to equivalent co-cultures without αPD-L1. h Analogous to c and f, showing CD69⁺ differences on CD8⁺ T-cells between αPD-L1- and mock-treated co-cultures. i Viability of TIS lymphomas sorted into CD115⁺ and CD115^– fractions before co-culture with T_TIS cells primed with unsorted, matched TIS lymphomas, or with T_naïve cells (n = 4 for T_TIS and T_naïve, or n = 3 for CD4⁺- and CD8⁺-T_TIS). Bars represent relative mean percentage of viable cells ± SEM compared to respective cell cultures without T-cells (b, d, e, g, i) or mean percentage difference of CD69⁺CD3⁺CD8⁺ cells ± SEM (f, h). j Viabilities of individual lymphomas as in b (n = 3) after 48-hr in non-matched co-cultures, i.e. target lymphomas were different from the T_TIS-priming lymphoma, with CD115^low T_TIS (n = 4), CD115^high T_TIS (n = 4; cf. Supplementary. Fig. 10f), T_Suv (n = 3; splenic T-cells primed by chemotherapy-exposed Suv39h1^–;bcl2 lymphomas), or T_naïve (n = 1). Bars show mean percentages ± SD. * two-sided P < 0.05 by paired (connecting lines) or one-sample t-test (b-i) or by unpaired t-test (j). See Supplementary Fig. 11a, b for combined data panels of b, c, e-h. See source Data file for exact P-values.