Abstract 723: Targeting phosphorylated p53 to elicit tumor-reactive T helper responses against head and neck squamous cell carcinoma

Abstract

Abstract The p53 is a DNA-binding and transcription activation domain containing tumor suppressor that upregulates growth arrest and apoptosis-related genes. In response to DNA damage, p53 is phosphorylated at multiple sites including serine 33 or 37. Additionally, abnormal phosphorylation of cellular proteins is a hallmark of malignant transformation. The human immune system is capable of distinguishing between the normal components and these posttranslational modifications. Therefore, the existence of posttranslational modifications increases the diversity of potential immune reactions to a determinant antigen. We identified phosphorylated peptide epitopes from tumor protein p53 that could elicit effective T helper-cell responses. Two epitope peptides, p5322-41/Phospho-S33 and p5322-41/Phospho-S37, induced T helper responses against tumor cells expressing phosphorylated p53 protein. Moreover, cisplatin and doxorubicin augmented the responses of such CD4+ T cells via upregulation of phosphorylated p53. Importantly, we elucidated the presence of peripheral blood lymphocytes specific for these peptide epitopes in the PBMCs of head and neck squamous cell cancer patients. These results predict that epitopes p5322-41/Phospho-S33 and p5322-41/Phospho-S37 are immunogenic for anti-tumor responses and could be beneficial for cancer immunotherapy. Citation Format: Kenzo Ohara, Takumi Kumai, Tatsuya Hayashi, Takayuki Ohkuri, Nobuyuki Bandoh, Hiroya Kobayashi, Yasuaki Harabuchi. Targeting phosphorylated p53 to elicit tumor-reactive T helper responses against head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 723.