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

Abstract：

BACKGROUND:Active 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. METHODS:Proteomic 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. FINDINGS:CD151 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. INTERPRETATION:The 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.

journal_name

EBioMedicine

journal_title

EBioMedicine

authors

Lin W,Liu J,Chen J,Li J,Qiu S,Ma J,Lin X,Zhang L,Wu J

doi

10.1016/j.ebiom.2019.10.025

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

133-144

issn

2352-3964

pii

S2352-3964(19)30689-9

journal_volume

49

pub_type

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