Immune deficiency augments the prevalence of p53 loss of heterozygosity in spontaneous tumors but not bi‐directional loss of heterozygosity in bone marrow progenitors

p53 loss of heterozygosity (LOH) is a frequent event in tumors of somatic and Li‐Fraumeni syndrome patients harboring p53 mutation. Here, we focused on resolving a possible crosstalk between the immune‐system and p53 LOH. Previously, we reported that p53 heterozygous bone‐marrow mesenchymal progenitor cells undergo p53 LOH in‐vivo . Surprisingly, the loss of either the wild‐type p53 allele or mutant p53 allele was detected with a three‐to‐one ratio in favor of losing the mutant allele. In this study, we examined whether the immune‐system can affect the LOH directionality in bone marrow progenitors. We found that mesenchymal progenitor cells derived from immune‐deficient mice exhibited the same preference of losing the mutant p53 allele as immune‐competent matched cells, nevertheless, these animals showed a significantly shorter tumor‐free survival, indicating the possible involvement of immune surveillance in this model. Surprisingly, spontaneous tumors of p53 heterozygous immune‐deficient mice exhibited a significantly higher incidence of p53 LOH compared to that observed in tumors derived of p53 heterozygous immune‐competent mice. These findings indicate that the immune‐system may affect the p53 LOH prevalence in spontaneous tumors. Thus suggesting that the immune‐system may recognize and clear cells that underwent p53 LOH, whereas in immune‐compromised mice, those cells will form tumors with shorter latency. In individuals with a competent immune‐system, p53 LOH independent pathways may induce malignant transformation which requires a longer tumor latency. Moreover, this data may imply that the current immunotherapy treatment aimed at abrogating the inhibition of cellular immune checkpoints may be beneficial for LFS patients.