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Table 2 Association of genome instability, alterations and immune therapy response

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

[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]