Table 1 The advantages and disadvantages of various neoantigens and associated cancers
Neoantigen classification | Sources | Advantages | Disadvantages | Cancers |
|---|---|---|---|---|
Genomic variants | Single-nucleotide variants (SNVs) mutation | Relatively high burden; Simple prediction | Rarely shared between patients; similar to self-antigen | Bladder cancer; Lung cancer (squamous and aseno); Melanoma; Glioblastoma |
Insertions and deletions (INDELs) mutation | More immunogenic; More potential targets per mutation; More dissimilar from self-antigen | Relatively low burden | Renal cell carcinomas (clear cell, chromophobe and papillary); MSI-H tumors | |
Genes fusion mutation | More immunogenic; More potential targets per mutation; More dissimilar from self-antigen; Shared targets between tumors | Relatively low burden | Chronic myeloid leukemia; Acute lymphocytic leukemia; Acute myelocytic leukemia; Sarcomas | |
Structural variants (SVs) mutation | High immunogenicity | Less well studied | Malignant pleural mesothelioma | |
Transcriptomic variants | Transcript alternative splicing | High immunogenicity; A large number of predicted targets | Less well studied | Squamous cell carcinoma of pancreas; Adenocarcinoma of lung |
Polyadenylation (PA) and RNA editing | Easy predication | Less well studied | Chronic lymphocytic leukemia | |
Allegedly non-coding regions | More potential targets; Relatively high burden | Less well studied; Fewer tools available | Acute lymphoblastic leukemias; Lung cancers | |
RNA splicing | More dissimilar from self-antigen; A large number of predicted targets | Fewer tools available; Current tools do not account for nonsense mediated decay (NMD); Not well validated in pre-clinical models; | Chronic lymphocytic leukemia; Acute myelocytic leukemia; Chronic myelocytic leukemia; Myelodysplastic syndrome | |
Proteomic variants | Post-translational modifications (PTMs) | Shared between patients | Less well studied | Non-small cell lung ancer; Leukemia; Renal cancer |
T cell epitopes associated with impaired peptide processing (PEIPP) | TEIPP-specific T cells can escape thymic selection | Less well studied; TAP-deficient tumors or Limited in HLA-I low | Lung cancer | |
Transporters associated with antigen processing (TAP) | High specificity | Less well studied; Fewer tools available | Acute myelocytic leukemia | |
Viral-derived neoantigens | Viral open reading frames (ORFs) or viral sequences or ERVs | High immunogenicity; Shared between patients; More dissimilar from self-antigen; Without apparent toxicity to normal tissues | Limited in specific tumors | Head and neck cancer; Merkel cell carcinoma; Nasopharyngeal carcinoma; Cervical cancer; Hepatocellular carcinoma; Anal cancers |
Tumor-testicular antigen | Testis or placenta | High immunogenicity; Strong immunogenicity; Not expressed in normal tissues except testicles and placenta | Less well studied; Limited in specific tumors | Testicular cancer; Germ cell tumor |
Tissue differentiation antigens and others | Melanoma or melanocytes or polysaccharides or lipid antigens | Most are presented by HLA-A2 | Less well studied; Cause damage to normal tissue; Inability to effectively present autoantigens | Melanoma; Some gastrointestinal tumors |