Wei SC, Duffy CR, Allison JP. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 2018;8(9):1069–86.
Akinleye A, Rasool Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J Hematol Oncol. 2019;12(1):92.
Jenkins RW, Barbie DA, Flaherty KT. Mechanisms of resistance to immune checkpoint inhibitors. Br J Cancer. 2018;118(1):9–16.
Hodi FS, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.
Hodi FS, et al. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2016;17(11):1558–68.
Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature. 2012;481(7381):287–94.
Burrell RA, et al. The causes and consequences of genetic heterogeneity in cancer evolution. Nature. 2013;501(7467):338–45.
Farmer H, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917–21.
Bryant HE, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434(7035):913–7.
Michèle R, et al. PARP inhibition: PARP1 and beyond. Nat Rev Cancer. 2010;10(4):293.
Matulonis UA, et al. Olaparib maintenance therapy in patients with platinum-sensitive, relapsed serous ovarian cancer and a BRCA mutation: overall survival adjusted for postprogression poly(adenosine diphosphate ribose) polymerase inhibitor therapy. Cancer. 2016;122(12):1844–52.
Sun C, et al. BRD4 inhibition is synthetic lethal with PARP inhibitors through the induction of homologous recombination deficiency. Cancer Cell. 2018;33(3):401–416.e8.
Javle M, Curtin NJ. The role of PARP in DNA repair and its therapeutic exploitation. Br J Cancer. 2011;105(8):1114–22.
Lemery S, Keegan P, Pazdur R. First FDA approval agnostic of cancer site — when a biomarker defines the indication. N Engl J Med. 2017;377(15):1409–12.
Topalian SL, et al. Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.
Taube JM, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20(19):5064–74.
Herbst RS, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563–7.
Mariathasan S, et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554(7693):544–8.
Weber JS, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16(4):375–84.
Robert C, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30.
Carbone DP, et al. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017;376(25):2415–26.
Bellmunt J, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376(11):1015–26.
Garcia-Diaz A, et al. Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Rep. 2017;19(6):1189–201.
Thiem A, et al. IFN-gamma-induced PD-L1 expression in melanoma depends on p53 expression. J Exp Clin Cancer Res. 2019;38(1):397.
Wu Y, et al. PD-L1 distribution and perspective for cancer immunotherapy-blockade, knockdown, or inhibition. Front Immunol. 2019;10:2022.
Hirsch FR, et al. PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol. 2017;12(2):208–22.
McLaughlin J, et al. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol. 2016;2(1):46–54.
Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med. 2017;377(25):2500–1.
Snyder A, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371(23):2189–99.
Van Allen EM, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2015;350(6257):207–11.
Hellmann MD, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093–104.
Hellmann MD, et al. Tumor mutational burden and efficacy of nivolumab monotherapy and in combination with ipilimumab in small-cell lung cancer. Cancer Cell. 2018;33(5):853–861.e4.
Rosenberg JE, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387(10031):1909–20.
Kao C, et al. Tumor mutational burden (TMB) as a predictive biomarker of immune checkpoint blockade (ICB) in metastatic solid tumors. J Clin Oncol. 2020;38(5_suppl):80.
McDermott DF, et al. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat Med. 2018;24(6):749–57.
Hanna GJ, et al. Frameshift events predict anti-PD-1/L1 response in head and neck cancer. JCI Insight. 2018;3(4):e98811.
McGrail DJ, et al. Multi-omics analysis reveals neoantigen-independent immune cell infiltration in copy-number driven cancers. Nat Commun. 2018;9(1):1317.
Riaz N, et al. Tumor and microenvironment evolution during immunotherapy with nivolumab. Cell. 2017;171(4):934–949.e16.
Endris V, et al. Measurement of tumor mutational burden (TMB) in routine molecular diagnostics: in silico and real-life analysis of three larger gene panels. Int J Cancer. 2019;144(9):2303–12.
Tumeh PC, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71.
Galon J, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.
Skoulidis F, et al. STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov. 2018;8(7):822–35.
Miao D, et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science. 2018;359(6377):801–6.
Braun DA, et al. Clinical validation of PBRM1 alterations as a marker of immune checkpoint inhibitor response in renal cell carcinoma. JAMA Oncol. 2019;5(11):1631–3.
Peng W, et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 2016;6(2):202–16.
George S, et al. Loss of PTEN is associated with resistance to anti-PD-1 checkpoint blockade therapy in metastatic uterine leiomyosarcoma. Immunity. 2017;46(2):197–204.
Gandhi L, et al. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med. 2018;378(22):2078–92.
Gainor JF, et al. EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: a retrospective analysis. Clin Cancer Res. 2016;22(18):4585–93.
Lisberg A, et al. A phase II study of pembrolizumab in EGFR-mutant, PD-L1+, tyrosine kinase inhibitor naive patients with advanced NSCLC. J Thorac Oncol. 2018;13(8):1138–45.
Zhao P, et al. Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J Hematol Oncol. 2019;12(1):54.
Iyer RR, et al. DNA mismatch repair: functions and mechanisms. Chem Rev. 2006;106(2):302–23.
Lynch HT, et al. Making sense of missense in Lynch syndrome: the clinical perspective. Cancer Prev Res. 2010;3(11):1371–4.
Mills AM, et al. The relationship between mismatch repair deficiency and PD-L1 expression in breast carcinoma. Am J Surg Pathol. 2018;42(2):183–91.
Ryan S, Jenkins MA, Win AK. Risk of prostate cancer in Lynch syndrome: a systematic review and meta-analysis. Cancer Epidemiol Biomark Prev. 2014;23(3):437–49.
Takamochi K, et al. DNA mismatch repair deficiency in surgically resected lung adenocarcinoma: microsatellite instability analysis using the Promega panel. Lung Cancer. 2017;110:26–31.
Pino MS, et al. Deficient DNA mismatch repair is common in Lynch syndrome-associated colorectal adenomas. J Mol Diagn. 2009;11(3):238–47.
Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993;260(5109):816–9.
Yamamoto H, Imai K, Perucho M. Gastrointestinal cancer of the microsatellite mutator phenotype pathway. J Gastroenterol. 2002;37(3):153–63.
Yamamoto H, et al. Gastric cancers of the microsatellite mutator phenotype display characteristic genetic and clinical features. Gastroenterology. 1999;116(6):1348–57.
Kato M, et al. DNA mismatch repair-related protein loss as a prognostic factor in endometrial cancers. J Gynecol Oncol. 2015;26(1):40–5.
Llosa NJ, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov. 2015;5(1):43–51.
Schwitalle Y, et al. Immune response against frameshift-induced neopeptides in HNPCC patients and healthy HNPCC mutation carriers. Gastroenterology. 2008;134(4):988–97.
Le DT, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.
Le DT, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–13.
Prasad V, Kaestner V, Mailankody S. Cancer drugs approved based on biomarkers and not tumor type-FDA approval of pembrolizumab for mismatch repair-deficient solid cancers. JAMA Oncol. 2018;4(2):157–8.
Yang RK, et al. Identification of biomarkers of immune checkpoint blockade efficacy in recurrent or refractory solid tumor malignancies. Oncotarget. 2020;11(6):600–18.
McGrail DJ, et al. Proteome instability is a therapeutic vulnerability in mismatch repair-deficient cancer. Cancer Cell. 2020;37(3):371–386.e12.
Strickland KC, et al. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget. 2016;7(12):13587–98.
Connor AA, et al. Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma. JAMA Oncol. 2017;3(6):774–83.
Jenzer M, et al. The BRCA2 mutation status shapes the immune phenotype of prostate cancer. Cancer Immunol Immunother. 2019;68(10):1621–33.
Panda A, et al. Role for immune checkpoint blockade in BRCA2-mutant prostate cancer. J Clin Oncol. 2019;37(8_suppl):59.
Green AR, et al. Clinical impact of tumor DNA repair expression and T-cell infiltration in breast cancers. Cancer Immunol Res. 2017;5(4):292–9.
Pellegrino B, et al. Homologous recombination repair deficiency and the immune response in breast cancer: a literature review. Transl Oncol. 2020;13(2):410–22.
Telli ML, et al. Association of tumor infiltrating lymphocytes with homologous recombination deficiency and BRCA1/2 status in patients with early triple-negative breast cancer: a pooled analysis. Clin Cancer Res. 2019:clincanres.0664.2019. https://clincancerres.aacrjournals.org/content/early/2019/12/03/1078-0432.CCR-19-0664.
Hugo W, et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell. 2016;165(1):35–44.
Disis ML, et al. Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer: phase 1b results from the JAVELIN solid tumor trial. JAMA Oncol. 2019;5(3):393–401.
David SS, O'Shea VL, Kundu S. Base-excision repair of oxidative DNA damage. Nature. 2007;447(7147):941–50.
Permata TBM, et al. Base excision repair regulates PD-L1 expression in cancer cells. Oncogene. 2019;38(23):4452–66.
Colebatch A, et al. The role of MYH and microsatellite instability in the development of sporadic colorectal cancer. Br J Cancer. 2006;95(9):1239–43.
Nielsen M, et al. Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas. BMC Cancer. 2009;9:184.
Cleaver JE, Lam ET, Revet I. Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity. Nat Rev Genet. 2009;10(11):756–68.
Aiello MM, et al. Excision repair cross complementation group 1 (ERCC-1) gene polymorphisms and response to nivolumab in advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2017;35(15_suppl):3032.
van Gool IC, et al. POLE proofreading mutations elicit an antitumor immune response in endometrial cancer. Clin Cancer Res. 2015;21(14):3347–55.
Howitt BE, et al. Association of polymerase e–mutated and microsatellite-instable endometrial cancers with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of PD-1 and PD-L1. JAMA Oncol. 2015;1(9):1319–23.
Mehnert JM, et al. Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer. J Clin Invest. 2016;126(6):2334–40.
Domingo E, et al. Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer: a retrospective, pooled biomarker study. Lancet Gastroenterol Hepatol. 2016;1(3):207–16.
Wang F, et al. Evaluation of POLE and POLD1 mutations as biomarkers for immunotherapy outcomes across multiple cancer types. JAMA Oncol. 2019;5(10):1504–6.
Mouw KW, et al. DNA damage and repair biomarkers of immunotherapy response. Cancer Discov. 2017;7(7):675–93.
Duijf PHG, et al. Mechanisms of genomic instability in breast cancer. Trends Mol Med. 2019;25(7):595–611.
McGrail DJ, et al. Defective replication stress response is inherently linked to the cancer stem cell phenotype. Cell Rep. 2018;23(7):2095–106.
Yarchoan M, et al. Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer. 2017;17(4):209–22.
Cerniglia M, et al. Association of DNA damage response and repair genes (DDR) mutations and microsatellite instability (MSI), PD-L1 expression, tumor mutational burden (TMB) in gastroesophageal cancers. J Clin Oncol. 2019;37(4_suppl):60.
Teo MY, et al. Alterations in DNA damage response and repair genes as potential marker of clinical benefit from PD-1/PD-L1 blockade in advanced urothelial cancers. J Clin Oncol. 2018;36(17):1685–94.
Chabanon RM, et al. Mutational landscape and sensitivity to immune checkpoint blockers. Clin Cancer Res. 2016;22(17):4309–21.
Li T, Chen ZJ. The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer. J Exp Med. 2018;215(5):1287–99.
Chen Q, Sun L, Chen ZJ. Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat Immunol. 2016;17(10):1142–9.
Motwani M, Pesiridis S, Fitzgerald KA. DNA sensing by the cGAS–STING pathway in health and disease. Nat Rev Genet. 2019;20(11):657–74.
Kwon J, Bakhoum SF. The cytosolic DNA-sensing cGAS–STING pathway in cancer. Cancer Discov. 2020;10(1):26–39.
Parkes EE, et al. Activation of STING-dependent innate immune signaling by S-phase-specific DNA damage in breast cancer. J Natl Cancer Inst. 2016;109(1):djw199.
Heijink AM, et al. BRCA2 deficiency instigates cGAS-mediated inflammatory signaling and confers sensitivity to tumor necrosis factor-alpha-mediated cytotoxicity. Nat Commun. 2019;10(1):100.
Lee J-M, et al. Safety and clinical activity of the programmed death-ligand 1 inhibitor durvalumab in combination with poly (ADP-ribose) polymerase inhibitor Olaparib or vascular endothelial growth factor receptor 1-3 inhibitor Cediranib in women’s cancers: a dose-escalation, phase I study. J Clin Oncol. 2017;35(19):2193–202.
Stewart RA, Pilie PG, Yap TA. Development of PARP and immune-checkpoint inhibitor combinations. Cancer Res. 2018;78(24):6717–25.
Konstantinopoulos PA, et al. Single-arm phases 1 and 2 trial of Niraparib in combination with pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma. JAMA Oncol. 2019;5(8):1141–9.
Shen J, et al. PARPi triggers the STING-dependent immune response and enhances the therapeutic efficacy of immune checkpoint blockade independent of BRCAness. Cancer Res. 2019;79(2):311–9.
Sen T, et al. Targeting DNA damage response promotes antitumor immunity through STING-mediated T-cell activation in small cell lung cancer. Cancer Discov. 2019;9(5):646–61.
Zhang Q, et al. Inhibition of ATM increases interferon signaling and sensitizes pancreatic cancer to immune checkpoint blockade therapy. Cancer Res. 2019;79(15):3940–51.
Wang Z, et al. Comutations in DNA damage response pathways serve as potential biomarkers for immune checkpoint blockade. Cancer Res. 2018;78(22):6486–96.
Li A, et al. Prospects for combining immune checkpoint blockade with PARP inhibition. J Hematol Oncol. 2019;12(1):98.