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 | Â | Not reported |