Table 2.

Advantages, disadvantages and relevant cancers for each class of neoantigens

Neoantigen classification	Sources	Advantages	Disadvantages	Relevant cancer
Genomic variants	Single-nucleotide variants (SNVs)	Simple prediction; relatively high burden	Similar to self-antigen; rarely shared between patients	Melanoma, glioblastoma, lung cancer (adeno and squamous), bladder cancer
	Insertions and deletion (INDEL) frameshift	More potential targets per mutation; more dissimilar from self-antigen; more immunogenic	Relatively low burden	MSI-H tumors, renal cell carcinomas (clear cell, papillary, and chromophobe)
	Fusion genes	More dissimilar from self-antigen; shared targets between tumors; more potential targets per mutation; more immunogenic	Relatively low burden	Acute myelocytic leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, sarcomas
	Chromosomal rearrangements	High immunogenicity	Less well studied	Malignant pleural mesothelioma
Transcriptomic variants	RNA splicing	A large number of predicted targets; More dissimilar from self-antigen	Fewer tools available; not well validated in pre-clinical models; current tools do not account for nonsense mediated decay (NMD)	Acute myelocytic leukemia, chronic myelomonocytic leukemia, chronic lymphocytic leukemia, myelodysplastic syndrome
	Polyadenylation (pA) and RNA editing	Easy prediction	Less well studied	Chronic lymphocytic leukemia
	Allegedly non-coding regions	Relatively high burden; more potential targets	Less well studied; fewer tools available	Acute lymphoblastic leukemias, lung cancers
Proteomic variants	Post-translational modifications (PTMs)	Shared between patients	Less well studied	leukemia, renal cancer, non-small cell lung cancer
	Proteasome processing	High specificity	Less well studied; fewer tools available	Acute myeloid leukemia
	T cell epitopes associated with impaired peptide processing (TEIPP)	TEIPP-specific T cells can escape thymic selection	Less well studied; limited in HLA-I low or TAP-deficient tumors	Lung cancer
Viral-derived neoantigens	Viral open reading frames	High immunogenicity; more dissimilar from self-antigen; shared between patients; without apparent toxicity to normal tissues.	Limited in specific tumors	Hepatocellular carcinoma, Merkel cell carcinoma, nasopharyngeal carcinoma, head and neck cancer, cervical cancer, anal cancers