Mutational burden and immune recognition of gliomas.
Journal
Current opinion in oncology
ISSN: 1531-703X
Titre abrégé: Curr Opin Oncol
Pays: United States
ID NLM: 9007265
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
entrez:
15
10
2021
pubmed:
16
10
2021
medline:
25
11
2021
Statut:
ppublish
Résumé
Recent evidence suggests high tumor mutational burden (TMB-H) as a predictor of response to immune checkpoint blockade (ICB) in cancer. However, results in TMB-H gliomas have been inconsistent. In this article, we discuss the main pathways leading to TMB-H in glioma and how these might affect immunotherapy response. Recent characterization of TMB-H gliomas showed that 'post-treatment' related to mismatch repair (MMR) deficiency is the most common mechanism leading to TMB-H in gliomas. Unexpectedly, preliminary evidence suggested that benefit with ICB is rare in this population. Contrary to expectations, ICB response was reported in a subset of TMB-H gliomas associated with constitutional MMR or polymerase epsilon (POLE) defects (e.g., constitutional biallelic MMRd deficiency). In other cancers, several trials suggest increased ICB efficacy is critically associated with increased lymphocyte infiltration at baseline which is missing in most gliomas. Further characterization of the immune microenvironment of gliomas is needed to identify biomarkers to select the patients who will benefit from ICB. Intrinsic molecular and immunological differences between gliomas and other cancers might explain the lack of efficacy of ICB in a subset of TMB-H gliomas. Novel combinations and biomarkers are awaited to improve immunotherapy response in these cancers.
Identifiants
pubmed: 34651608
doi: 10.1097/CCO.0000000000000787
pii: 00001622-202111000-00013
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
626-634Subventions
Organisme : NCI NIH HHS
ID : R01 CA188288
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA163205
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA165962
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Références
Ostrom Q, Gittleman H, Liao P, et al. Neuro-Oncology CBTRUS Statistical Report: primary brain and other central nervous system tumors diagnosed in the United 2018; 19:1–88.
Wen PY, Weller M, Lee EQ, et al. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions. Neuro Oncol 2020; 22:1073–1113.
Weller M, van der Bent M, Preusser M, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol 2021; 18:170–186.
Weller M, van den Bent M, Tonn J, et al. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 2017; 18:e315–e329.
Touat M, Idbaih A, Sanson M, et al. Glioblastoma targeted therapy: updated approaches from recent biological insights. Ann Oncol 2017; 7:1457–1472.
Chan TA, Yarchoan M, Jaffee E, et al. Development of tumor mutation burden as an immunotherapy biomarker: Utility for the oncology clinic. Ann Oncol 2019; 30:44–56.
Cristescu R, Mogg R, Ayers M, et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science (80−) 2018; 362:
Yarchoan M, Hopkins A, Jaffee E. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med 2019; 377:2500–2501.
Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in nonsmall cell lung cancer. Science (80-) 2016; 348:124–128.
Mcgranahan N, Furness AJS, Rosenthal R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science (80-) 2016; 351:1463–1469.
Keenan TE, Burke KP, Allen EM Van, et al. Genomic correlates of response to immune checkpoint blockade. Nat Med 2019; 25:389–402.
Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol 2020; 21:1353–1365.
Campbell B, Light N, Abrizio D, et al. Comprehensive analysis of hypermutation in human cancer. Cell 2017; 171:1042–1056.
Touat M, Li YY, Boynton AN, et al. Mechanisms and therapeutic implications of hypermutation in gliomas. Nature 2020; 580:517–523.
Thorsson V, Gibbs D, Brown S, et al. The immune landscape of cancer. Immunity 2018; 48:812–830.
Gromeier M, Brown MC, Zhang G, et al. Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy. Nat Commun 2021; 12:1–7.
Bouffet E, Larouche V, Campbell BB, et al. Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J Clin Oncol 2016; 34:2206–2211.
Lukas R, Rodon J, Becker K, et al. Clinical activity and safety of atezolizumab in patients with recurrent glioblastoma. J Neurooncol 2018; 140:317–328.
Sathornsumetee S, Nunta-aree S, Cheunsuchon P, et al. Immune checkpoint inhibitor in recurrent hypermutated glioblastoma with POLE mutation. Neuro-Oncology Adv 2021; 3:vdab093.
Morgenstern D, Sudhaman S, Das A, et al. Mutation and Microsatellite Burden Predict Response to PD-1 Inhibition in Children with Germline DNA Replication Repair Deficiency, 2021, PREPRINT (Version 1) available at Research Square https://doi.org/10.21203/rs.3.rs-155292/v1 .
Rittberg R, Harlos C, Rothenmund H, et al. Immune checkpoint inhibition as primary adjuvant therapy for an IDH1-mutant anaplastic astrocytoma in a patient with CMMRD: A case report—usage of immune checkpoint inhibition in CMMRD. Curr Oncol 2021; 28:757–766.
McCord M, Lukas R, Amidei C. Disappearance of MMR-deficient subclones after Controlled IL-12 and PD-1 inhibition in a glioma patient. Neuro-Oncol Adv 2021; vdab045:1–31.
Anghileri E, Di Ianni N, Paterra R, et al. High tumor mutational burden and T-cell activation are associated with long-term response to anti-PD1 therapy in Lynch syndrome recurrent glioblastoma patient. Cancer Immunol Immunother 2021; 70:831–842.
Lombardi G, Barresi V, Indraccolo S, et al. Pembrolizumab activity in recurrent high-grade gliomas with partial or complete loss of mismatch repair protein expression: a monocentric, observational and prospective pilot study. Cancers 2020; 12:1–14.
Guo X, Wang S, Wang YMW. Anti-PD-1 plus anti-VEGF therapy in multiple intracranial metastases of a hypermutated, IDH wild-type glioblastoma. Neuro Oncol 2021; 23:699–701.
Johanns TM, Miller CA, Dorward IG, et al. Immunogenomics of Hypermutated Glioblastoma: a Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy. Cancer Discov 2017; 6:1230–1236.
AlHarbi M, Ali Mobark N, AlMubarak L, et al. Durable response to nivolumab in a pediatric patient with refractory glioblastoma and constitutional biallelic mismatch repair deficiency. Oncologist 2018; 23:1401–1406.
Larouche V, Atkinson J, Albrecht S, et al. Sustained complete response of recurrent glioblastoma to combined checkpoint inhibition in a young patient with constitutional mismatch repair deficiency. Pediatr Blood Cancer 2018; 65:4–5.
Alexandrov LB, Nik-zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature 2014; 500:415–421.
Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature 2009; 458:719–724.
Alexandrov LB, Kim J, Haradhvala NJ, et al. The repertoire of mutational signatures in human cancer. Nature 2020; 578:94–101.
Vogelstein B, Papadopoulos N, Velculescu V, et al. Cancer genome landscapes. Science (80−) 1986; 233:1246–1258.
Jiricny J. The multifaceted mismatch-repair system. Nat Rev Mol Cell Biol 2006; 7:335–346.
Hugo W, Zaretsky JM, Sun L, et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell 2016; 165:35–44.
Rizvi H, Sanchez-Vega F, La K, et al. Molecular determinants of response to antiprogrammed cell death (PD)-1 and antiprogrammed death-ligand 1 (PD-L1) blockade in patients with nonsmall-cell lung cancer profiled with targeted next-generation sequencing. J Clin Oncol 2018; 36:633–641.
Miao D, Margolis CA, Vokes NI, et al. Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors. Nat Genet 2018; 50:1271–1281.
Alnahhas I, Rayi A, Ong S, et al. Management of gliomas in patients with Lynch syndrome. Neuro Oncol 2021; 23:167–168.
Vande Perre P, Siegfried A, Corsini C, et al. Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma. Fam Cancer 2019; 18:173–178.
Erson-Omay E, Çaglayan A, Schultz N, et al. Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis. Neuro Oncol 2015; 17:1356–1364.
Pollo B, Patané M, Calatozzolo C, Paterra R. Giant cell glioblastomas: analysis of mismatch-repair (MMR) proteins expression, polimerase ε (POLE) mutations and their role in tumor immunoresponse. Neuro Oncol 2018; suppl_6:vi165.
Bakry D, Aronson M, Durno C, et al. Genetic and clinical determinants of constitutional mismatch repair deficiency syndrome: report from the constitutional mismatch repair deficiency consortium. Eur J Cancer 2014; 50:987–996.
Aronson M, Colas C, Shuen A, et al. Diagnostic criteria for constitutional mismatch repair deficiency (CMMRD): recommendations from the international consensus working group. J Med Genet 2021; jmedgenet-2020-107627.
Guerrini-Rousseau L, Varlet P, Colas C, et al. Constitutional mismatch repair deficiency-associated brain tumors: report from the European C4CMMRD consortium. Neuro-Oncol Adv 2019; 1:1–13.
Lavoine N, Colas C, Muleris M, et al. Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort. J Med Genet 2014; 52:770–778.
Vasen H, Ghorbanoghli Z, Bourdeaut F, et al. Guidelines for surveillance of individuals with constitutional mismatch repair-deficiency proposed by the European Consortium ‘Care for CMMR-D’ (C4CMMR-D). J Med Genet 2014; 51:283–293.
Shlien A, Campbell BB, De Borja R, et al. Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers. Nat Genet 2015; 47:257–262.
Dodgshun AJ, Fukuoka K, Edwards M, et al. Germline-driven replication repair-deficient high-grade gliomas exhibit unique hypomethylation patterns. Acta Neuropathol 2020; 140:765–776.
Therkildsen C, Ladelund S, Rambech E, et al. Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome. Eur J Neurol 2015; 22:717–724.
Suwala AK, Stichel D, Schrimpf D, et al. Primary mismatch repair deficient IDH-mutant astrocytoma (PMMRDIA) is a distinct type with a poor prognosis. Acta Neuropathol 2021; 141:85–100.
Hunter C, Smith R, Cahill P, Hypermutation Phenotype A. Somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res 2006; 66:3987–3991.
Yu Y, Villanueva-Meyer J, Grimmer MR, Hilz S. Temozolomide-induced hypermutation is associated with distant recurrence and reduced survival after high-grade transformation of low-grade IDH-mutant gliomas. Neuro Oncol 2021; noab081.
Cahill DP, Levine KK, Betensky RA, et al. Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment. Clin Cancer Res 2007; 13:2038–2045.
Yip S, Miao J, Cahill D, Iafrate J. MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance. Clin Cancer Res 2009; 15:4622–4629.
Johnson B, Mazor T, Chibo H, Barnes M. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science2 2014; 343:189–193.
van Thuijl H, Mazor T, Johnson B, Fouse S. Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment. Acta Neuropathol 2015; 129:597–607.
Caccese M, Ius T, Simonelli M, et al. Mismatch-repair protein expression in high-grade gliomas: a large retrospective multicenter study. Int J Mol Sci 2020; 21:1–12.
Dunn GP, Cloughesy TF, Maus MV, et al. Emerging immunotherapies for malignant glioma: from immunogenomics to cell therapy. Neuro Oncol 2020; 22:1425–1438.
Fu D, Calvo J, Samson L. SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents. Nat Rev Cancer 2013; 12:104–120.
Esteller M, Garcia-Foncillas J, Andion E. Inactivation of the dna-repair gene mgmt and the clinical response of gliomas to alkylating agents. N Engl J Med 2000; 343:1350–1354.
Hegi ME, Diserens A-C, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005; 352:997–1003.
Ratovomanana T, Cohen R, Svrcek M. Performance of next generation sequencing for the detection of microsatellite instability in colorectal cancer with deficient DNA mismatch repair. Gastroenterology 2021; S0016-5085(21)):02977-2.
Indraccolo S, Lombardi G, Fassan M, et al. Genetic, epigenetic, and immunologic profiling of MMR-deficient relapsed glioblastoma. Clin Cancer Res 2019; 25:1828–1837.
Hodges TR, Ott M, Xiu J, et al. Mutational burden, immune checkpoint expression, and mismatch repair in glioma: Implications for immune checkpoint immunotherapy. Neuro Oncol 2017; 19:1047–1057.
Kloor M, von Knebel Doeberitz M. The immune biology of microsatellite-unstable cancer. Trends Cancer 2016; 2:121–133.
Sun J, Wang C, Zhang Y, et al. Genomic signatures reveal DNA damage response deficiency in colorectal cancer brain metastases. Nat Commun 2019; 10:18–20.
Dunn IF, Du Z, Touat M, et al. Mismatch repair deficiency in high-grade meningioma: a rare but recurrent event associated with dramatic immune activation and clinical response to PD-1 blockade. JCO Precis Oncol 2018; 1–12.
Berends MJW, Wu Y, Sijmons RH, et al. Molecular and clinical characteristics of MSH6 variants: An analysis of 25 index carriers of a germline variant. Am J Hum Genet 2002; 70:26–37.
Yang G, Scherer SJ, Shell SS, et al. Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility. Cancer Cell 2004; 6:139–150.
Geng H, Sakato M, DeRocco V, et al. Biochemical analysis of the human mismatch repair proteins hMutSα MSH2 G674A-MSH6 and MSH2-MSH6 T1219D. J Biol Chem 2012; 287:9777–9791.
Huang K, Mashl RJ, Wu Y, et al. Pathogenic germline variants in 10,389 adult cancer. Cell 2019; 173:355–370.
Fiala EM, Jayakumaran G, Mauguen A, et al. Prospective pan-cancer germline testing using MSK-IMPACT informs clinical translation in 751 patients with pediatric solid tumors. Nat Cancer 2021; 2:357–365.
Barthel F, Johnson K. The Glioma Longitudinal Analysis (GLASS) Consortium. Longitudinal molecular trajectories of diffuse glioma in adults. Nature 2019; 576:112–120.
van den Bent MJ, Tesileanu CMS, Wick W, et al. Adjuvant and concurrent temozolomide for 1p/19q nonco-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): second interim analysis of a randomised, open-label, phase 3 study. Lancet Oncol 2021; 22:813–823.
Stupp R, Mason WP, van den Bent M, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352:987–996.
Martin LM, Marples B, Coffey M, et al. DNA mismatch repair and the DNA damage response to ionizing radiation: making sense of apparently conflicting data. Cancer Treat Rev 2010; 36:518–527.
Wedge SR, Porteous JK, May BL, et al. Potentiation of temozolomide and BCNU cytotoxicity by O6-benzylguanine: a comparative study in vitro. Br J Cancer 1996; 73:482–490.
Wedge SR, Porteous JK, Newlands ES. 3-Aminobenzamide and/or O6-benzylguanine evaluated as an adjuvant to temozolomide or BCNU treatment in cell lines of variable mismatch repair status and O6-alkylguanine-DNA alkyltransferase activity. Br J Cancer 1996; 74:1030–1036.
Herrlinger U, Tzaridis T, Mack F. Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial. Lancet 2019; 393:678–688.
Higuchi F, Nagashima H, Ning J. Restoration of temozolomide sensitivity by PARP inhibitors in mismatch repair deficient glioblastoma is independent of base excision repair. Clin Cancer Res 2020; 26:1690–1699.
Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 2014; 371:2189–2199.
Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015; 372:2018–2028.
Le DT, Durham JN, Smith KN, et al. Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade. Science (80-) 2017; 357:409–413.
Samstein RM, Lee CH, Shoushtari A. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 2017; 176:139–148.
Cho JJ, Stewart JM, Drashansky T. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science (80-) 2015; 350:207–211.
McGrail DJ, Pilié PG, Rashid NU, et al. High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types. Ann Oncol 2021; 32:661–672.
Reardon DA, Brandes AA, Omuro A, et al. Effect of Nivolumab vs Bevacizumab in patients with recurrent glioblastoma: the checkmate 143 phase 3 randomized clinical trial. 2020;6(7):1003–1010. JAMA Oncol 2020; 6:1003–1010.
Gejman RS, Chang AY, Jones HF, et al. Rejection of immunogenic tumor clones is limited by clonal fraction. Elife 2018; 7:1–22.
Hodel KP, De Borja R, Henninger EE, et al. Explosive mutation accumulation triggered by heterozygous human Pol ε proofreading-deficiency is driven by suppression of mismatch repair. Elife 2018; 7:1–25.
Aslan K, Turco V, Blobner J, et al. Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas. Nat Commun 2020; 11:1–14.
Chiocca EA, Yu JS, Lukas RV, et al. Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial. Sci Transl Med 2020; 11: