Table 2.
Association of genome instability, alterations and immune therapy 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 | [58, 59] |
| 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 | [57, 61] |
| VHL, SETD2, BAP1, KDM5C, FHIT defects | Frameshift indels/elevated proportion vs SNVs | Medium load/elevated number of strong binders | Checkpoint blockade responsive | [40, 62, 63] |
| 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 | [65, 66] |