From: Neoantigens and genome instability: impact on immunogenomic phenotypes and immunotherapy response
Source of genome instability | Mutational profile/burden | Neoantigen load | Response to immunotherapy | References |
---|---|---|---|---|
POLE mutation (germline or somatic) | Single nucleotide variants (SNVs)/ultra-hypermutated | High load | Checkpoint blockade responsive | |
BRCA1/2 mutation (germline) | Frameshift indels/elevated proportion vs SNVs | Medium load/elevated number of strong binders | Checkpoint blockade responsive | [60] |
Lynch syndrome (MSH1, MLH2, MLH6, PMS2) | SNVs and indels/hypermutated | High load/elevated number of strong binders | Checkpoint blockade responsive, personalized vaccine responsive | |
VHL, SETD2, BAP1, KDM5C, FHIT defects | Frameshift indels/elevated proportion vs SNVs | Medium load/elevated number of strong binders | Checkpoint blockade responsive | |
Xeroderma pigmentosum defect (DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, POLH, XPA, or XPC) | SNVs/ultra-hypermutated | High load | Checkpoint blockade responsive | [64] |
Constitutional mismatch repair deficiency syndrome (CMMRD): biallelic germline mutations in Lynch syndrome genes (MLH1, MSH2, MSH6, PMS2) | SNVs/hypermutated | High load | Checkpoint blockade responsive |