Figure 5.
p53-induced senescence increases natural killer cell infiltration into the tumors. (A–C) Rag2−/− mice were injected subcutaneously with 2 × 106 liver tumor cells with inducible p53. 10 d later, tumors were harvested from one group of mice (day 0), whereas other groups continued with (p53-on) or without (p53-off) doxycycline treatment for an additional 4 or 8 d. Single cell tumor suspensions were stained with CD45 and NKp46 antibodies to determine the percentages of infiltrating hematopoietic cells (CD45+) among all cells in the tumors (A), the percentages of NK cells (NKp46+) among the infiltrating hematopoietic cells (B), and the percentage of NK cells among all cells in the tumors. The data are representative of two to three independent experiments. (D and E) Established tumors in Rag2−/− or Rag2−/−Klrk1−/− mice were treated or not with doxycycline. 8 d later, single cell tumor suspensions were stained as described in A–C to determine the percentages of infiltrating CD45+ cells among all cells in the tumors (D) and the percentages of NK cells among all cells in the tumors (E). Values represent means ± SEM (n = 8 mice per group for A and 5 mice per group for B–E). Two-way ANOVA and Bonferroni’s tests were performed. The data are representative of two to three independent experiments. *, P < 0.05; ***, P < 0.001.