Tumor neoantigens: from basic research to clinical applications

Abstract

Tumor neoantigen is the truly foreign protein and entirely absent from normal human organs/tissues. It could be specifically recognized by neoantigen-specific T cell receptors (TCRs) in the context of major histocompatibility complexes (MHCs) molecules. Emerging evidence has suggested that neoantigens play a critical role in tumor-specific T cell-mediated antitumor immune response and successful cancer immunotherapies. From a theoretical perspective, neoantigen is an ideal immunotherapy target because they are distinguished from germline and could be recognized as non-self by the host immune system. Neoantigen-based therapeutic personalized vaccines and adoptive T cell transfer have shown promising preliminary results. Furthermore, recent studies suggested the significant role of neoantigen in immune escape, immunoediting, and sensitivity to immune checkpoint inhibitors. In this review, we systematically summarize the recent advances of understanding and identification of tumor-specific neoantigens and its role on current cancer immunotherapies. We also discuss the ongoing development of strategies based on neoantigens and its future clinical applications.

The Intriguing History of Cancer Immunotherapy

“…Being highly immunogenic, they can activate CD4+ and CD8+ immune response, providing a perfect target for T cell based cancer immunotherapies (81). Several preclinical studies have already shown the feasibility and efficacy of neoantigen-targeting cancer vaccines in mice models of tumors, for example colon carcinoma, melanoma, glioma and sarcoma (84). Although still in very early stages, approaches combining neoantigens-based therapies with other types of immunotherapy, such as checkpoint inhibitors, as well as conventional treatments, are already ongoing (83,84).…”

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

“…Thus, neoantigen-based cancer vaccines, including neoantigen vaccine, peptide vaccine, DNA vaccine, RNA vaccine, and DC vaccine, are developed to overcome these limitations in cancer immunotherapy. Some of these vaccines have been investigated in clinical trials (109). In patients with PD-L1 + TNBC tissues, the overall response rate to ICB therapy ranges from 10 to 18.5% (110).…”

Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges

“…However, inter-individual variations in passenger mutations among patients make their detection difficult using conventional technology. Recently, the development of next-generation sequencers enables easier detection through wholeexome analysis [73,74]. In addition, gene fusions are also identified as a source of immunogenic Thus, tumor-specific antigens originating from cancer cell-specific gene mutation exist as nonself, because they are absent in normal cells and present in cancer cells alone and are called "neoantigens."…”

“…However, inter-individual variations in passenger mutations among patients make their detection difficult using conventional technology. Recently, the development of next-generation sequencers enables easier detection through whole-exome analysis [73,74]. In addition, gene fusions are also identified as a source of immunogenic neoantigens which can mediate anticancer immune responses [75,76].…”