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Table 1 Summary of the relationships between DDR defects and ICB response

From: Role of DNA repair defects in predicting immunotherapy response

DDR defects

Tumor types

Criteria

Immunologic features

ICB response

MSI/dMMR

Colon, endometrial, gastric, ovarian

Germline mutations in DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2

Increased TMB, neoantigen load, TILs, and expression of PD-1 or PD-L1

Patients with MMR-deficient tumors had improved response rate to anti-PD-1 therapy: NCT01876511

Ongoing trials: NCT02563002, NCT02912572, NCT02899793, NCT03150706, NCT03435107

HR defects

Ovarian, breast, prostate, pancreatic

Germline mutations in BRCA1 or BRCA2

Increased neoantigen load, TILs, and expression of PD-1 or PD-L1

ICB therapy in HR deficient cancers has shown conflicting results: NCT01772004, Refs. [71, 75]

Ongoing trials: NCT03025035, NCT03428802, NCT02571725, NCT03101280, NCT02849496

POLD1/POLE mutations

Endometrial, colon,

Germline mutations in POLD1 or POLE

Increased TMB, neoantigen load, TILs, and effector cytokine levels

Ongoing trials: NCT02912572, NCT02899793, NCT03150706, NCT03435107, NCT03428802

BER deficiency

Colon, breast, endometrial

Germline mutations in MUTYH

Increased neoantigen load and PD-L1 expression

Not reported

NER defects

Lung

Single nucleotide polymorphisms in ERCC1

 

Not reported