p53-deficient lymphomas escape immunosurveillance. (A) Transplantation of tumor cell lines with indicated second hit, obtained from Eμ-myc mice, in C57BL/6 and Tyk2^−/− recipient mice. The TYK2-associated immune defect led to reduced survival time of the recipient mice irrespectively of the second hit found in transplanted tumor cells. (C57BL/6 − p53, n = 8; and Tyk2 − p53, n = 9; C57BL/6 − BCL-2, n = 15; and Tyk2 − BCL-2, n = 12). Only 2 combinations meet the criterion of statistical significance (C57BL/6 − BCL-2 vs Tyk2 − BCL-2; P = .042). (B) Transplantation of Eμ-myc/vav-bcl-2 or Eμ-myc/p53^+/− splenocytes into C57BL/6, CD8⁺, or NK cell–depleted recipient mice. Immune cell depletion does not alter the survival time of mice receiving splenocytes from Eμ-myc/p53^+/− mice. In contrast NK-cell depletion as well as CD8⁺-cell depletion reduces the survival of recipient mice significantly (wt < BCL-2 vs CD8⁺ < BCL-2, P < .001; wt < BCL-2 vs NK < BCL-2, P < .001). Depl indicates depleted. (C) Mean survival of mice (C57BL/6 wt, CD8⁺-cell or NK-cell depleted) that received a transplant with Eμ-myc/vav-bcl-2 or Eμ-myc/p53^+/− splenocytes. This figure is for better illustration of findings described in panel B. Asterisks indicate level of statistical significance (***P ≤ .001). (D) Schematic drawing of our working hypothesis. Tumor cells overexpressing BCL-2 are recognized or destroyed by the immune system more easily than the ones harboring defects in the p19-p53 signaling pathway.