Peptides of tetraspanin oncoprotein CD151 trigger active immunity against primary tumour and experimental lung metastasis.

Abstract

BackgroundActive immunotherapy is an effective, long-lasting, cheap, and safe approach to suppress cancer progression; however, the key issue is to develop appropriate tumour vaccines. Oncoproteins are up-regulated under various stress conditions and promote cell survival. Oncoproteins and their immunogenic domains could serve well as tumour vaccines and prime the hosts’ active anti-tumour immunity.MethodsProteomic and bioinformatic analyses were performed to identify potential tumour associated antigens (TAAs). Then, peptides derived from CD151 were designed and synthesized according to the major histocompatibility complex (MHC) I binding and immunogenicity. Cytotoxicity assay, flow cytometry, immunohistochemistry, and in vivo bioluminescence imaging were performed to assess the active anti-tumour immunity triggered by CD151 peptides in H22 primary hepatoma and experimental 4T1 breast cancer lung metastasis models.FindingsCD151 was identified as an ideal TAA based on proteomic and bioinformatic analyses. CD151 peptides as tumour vaccines triggered active anti-tumour immunity against H22 hepatoma and the lung metastasis of 4T1 breast cancer in two mouse models through the activation of CD8+IFNγ+ lymphocytes and the subsequent targeted cytotoxicity. Further, the peptides suppressed the negative regulators, myeloid-derived suppressor cells. Survival was prolonged for mice with lung metastases from CD151 peptide-immunised groups.InterpretationThe up-regulated oncoproteins in 8 Gy-irradiated tumour cells are good candidates for designing immunogenic peptides as tumour vaccines. Anti-tumour active immunity primed by peptides from CD151 may be an effective and safe approach to suppress cancer progression.