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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1456209
This article is part of the Research Topic Identification and Characterization of Neoantigens for Cancer Immunotherapy View all 8 articles

In silico neoantigen screening and HLA multimer-based validation identify immunogenic neopeptide in multifocal lung adenocarcinoma

Provisionally accepted
Xin Wang Xin Wang 1Lang Jiang Lang Jiang 1Juan Zhao Juan Zhao 1Mi Wu Mi Wu 1Jin Xiong Jin Xiong 2Xiongwen Wu Xiongwen Wu 1*Xiufang Weng Xiufang Weng 1*
  • 1 Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 2 Department of Blood Transfusion, Tongji Hospital, Wuhan, Hubei Province, China

The final, formatted version of the article will be published soon.

    Background Mutations commonly occur in cancer cells, arising neoantigen as potential targets for personalized immunotherapy of lung adenocarcinoma (LUAD). However, the substantial heterogeneity observed among individuals and distinct foci within the same patient presents significant challenges in formulating immunotherapy strategies. The aim of the work is to characterize the mutation pattern and identify neopeptides across different patients and diverse foci within the same patients with LUAD.Methods Seven lung adenocarcinoma samples and matched tissues/ blood are collected from 4 patients with LUAD for whole exome sequencing, mutation signature analysis, HLA binding prediction and neoantigen screening. Dimeric HLA-A2 molecules were prepared by Bac-to-Bac baculovirus expression system to establish a T cell stimulation system based on HLA-A2-coated artificial antigen-presenting cells for the validation of immunogenic neopeptides.Results Similar mutation pattern with predominant missense mutation and high tumor mutation burden was observed across individuals with lung adenocarcinomas and between non-invasive and invasive foci. We screened and identified 3 consistent mutated genes among 100 top genes with highest mutation scores contributed across 4 patients, and 3 mutated peptides among 30 with highest HLA-A2 binding affinity distributed in at least 2 out of 4 foci in the same patient. Notably, LUAD-7-MT peptide encoded by NANOGNB demonstrated higher immunogenicity in promoting CD8+ T cells proliferation and IFN-γ secretion than the corresponding wildtype peptide.This study provides an in-depth analysis of mutation characteristics of LUAD and establishes a neoantigen screening and validation system for identifying immunogenicity neopeptide across individual patients and diverse foci in the same patient with multifocal LUAD.

    Keywords: Neopeptide screening1, Multifocal lung adenocarcinoma2, NANOGNB3, immunogenicity neopeptide4, artificial antigen-presenting cells5. (Min.5-Max. 8)

    Received: 28 Jun 2024; Accepted: 04 Nov 2024.

    Copyright: © 2024 Wang, Jiang, Zhao, Wu, Xiong, Wu and Weng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xiongwen Wu, Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Xiufang Weng, Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

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