Микросателлитная нестабильность как уникальная характеристика опухолей и предиктор эффективности иммунотерапии
Автор: Трякин А. А., Федянин М. Ю., Цуканов А. С., Шелыгин Ю. А., Покатаев И. А., Игнатова Е. О., Хакимова Г. Г., Фролова М. А., Тюляндин С. А.
Журнал: Злокачественные опухоли @malignanttumors
Рубрика: Обзоры и аналитика
Статья в выпуске: 4 т.9, 2019 года.
Бесплатный доступ
Дефицит системы репарации неспаренных оснований представляет собой уникальное молекулярное нарушение, встречающееся в большинстве видах опухолей и проводящее к формированию в них микросателлитной нестабильности (MSI). Возникновение гипермутированного фенотипа и связанная с ним высокая иммуногенность обуславливает в целом более благоприятный прогноз данных опухолей, а также высокую чувствительность к иммунотерапии ингибиторами контрольных точек иммунного ответа. В данной обзорной статье представлены современные представления по диагностике, прогностической и предиктивной значимости MSI при различных опухолях, а также об эффективности их иммунотерапии.
Дефицит системы неспаренных оснований, микросателлитная нестабильность, иммунотерапия, ниволумаб, пембролизумаб, ипилимумаб
Короткий адрес: https://sciup.org/140249286
IDR: 140249286 | DOI: 10.18027/2224-5057-2019-9-4-59-69
Список литературы Микросателлитная нестабильность как уникальная характеристика опухолей и предиктор эффективности иммунотерапии
- GM., Li. Mechanisms and functions of DNA mismatch repair. Cell Res 2008; 18: 85 - 98.
- Цуканов А. С., Шелыгин Ю. А., Семенов Д. А., с соавт. Синдром Линча. Современное состояние проблемы. Медицинкая генетика, 2017. Т. 16. № 2. С 11 - 18.
- Bonadona V, Bonaïti B, Olschwang S, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 2011;30:2304 - 10.
- Alarcon F, Lasset C, Carayol J, et al. Estimating cancer risk in HNPCC by the BRL method. Eur J Hum Genet 2007;15:831 - 6.
- Barrow E, Robinson L, Alduaij W, et al. Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations. Clin Genet 2009;75:141 - 9.
- Engel C, Loeffler M, Steinke V, et al. Risks of less common cancers in proven mutation carriers with lynch syndrome. J Clin Oncol 2012;30: 4409 - 15.
- Latham A., Srinivasan P, Kemel Y, et al. Microsatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer. J Clin Oncol 2019, 37 (4): 286 - 299.
- Boland C. R., Goel A. Microsatellite instability in colorectal cancer. Gastroenterology 2010;138 (6):2073 - 87.
- Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017; 357: 409 - 413.
- Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372: 2509 - 2520.
- Dolcetti R, Viel A, Doglioni C, et al. High prevalence of activated intraepithelial cytotoxic T lymphocytes and increased neoplastic cell apoptosis in colorectal carcinomas with microsatellite instability. Am J Pathol 1999; 154: 1805 - 1813.
- Llosa NJ, Cruise M, Tam A, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov 2015; 5: 43 - 51.
- Lal N, Beggs AD, Willcox BE, et al. An immunogenomic stratification of colorectal cancer: Implications for development of targeted immunotherapy. Oncoimmunology. 2015 Apr 2;4 (3):e976052.
- Llosa N. J., Cruise M., Tam A. 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.
- Fusi A., Festino L., Botti G. et al. PD-L1 expression as a potential predictive biomarker. Lancet Oncol 2015;16 (13):1285 - 7.
- Guinney J, Dienstmann R, Wang X, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov;21 (11):1350 - 6.
- Network., Cancer Genome Atlas Research. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513, 202 - 209 (2014).
- Kandoth C, Schultz N, Cherniack AD, et al. Integrated genomic characterization of endometrial carcinoma. Nature 497:67 - 73, 2013.
- Umar A, Boland CR, Terdiman JP, et al. Revised bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004; 96: 261 - 268.
- C Luchini, F Bibeau, M J L Ligtenberg, et al. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1 / PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol 2019, 30 (8): 1232 - 1243.
- Colle R, Cohen R, Cochereau D, et al. Immunotherapy and patients treated for cancer with microsatellite instability. Bull Cancer 2017; 104: 42 - 51.
- J., Shia. Evolving approach and clinical significance of detecting DNA mismatch repair deficiency in colorectal carcinoma. Semin Diagn Pathol 2015; 32: 352 - 361.
- TA., Mills AM and Longacre. Lynch syndrome screening in the gynecologic tract: current state of the art. Am J Surg Pathol 2016; 40: e35-44.
- Mills AM, Sloan EA, Thomas M, et al. Clinicopathologic comparison of lynch syndrome-associated and "Lynch-like" endometrial carcinomas identified on universal screening using mismatch repair protein immunohistochemistry. Am J Surg Pathol 2016; 40: 155 - 165.
- Gan C, Love C, Beshay V, et al. Applicability of next generation sequencing technology in microsatellite instability testing. Genes 2015; 6: 46 - 59.
- Vanderwalde A, Spetzler D, Xiao N, et al. Microsatellite instability status determined by next-generation sequencing and compared with PD-L1 and tumor mutational burden in 11,348 patients. Cancer Med 2018; 7: 746 - 756.
- Hause RJ, Pritchard CC, Shendure J, Salipante SJ. Classification and characterization of microsatellite instability across 18 cancer types. Nat Med. 2016 Nov;22 (11):1342 - 1350.
- Zaanan A, Shi Q, Taieb J, et al. Role of Deficient DNA Mismatch Repair Status in Patients With Stage III Colon Cancer Treated With FOLFOX Adjuvant Chemotherapy: A Pooled Analysis From 2 Randomized Clinical Trials. JAMA Oncol. 2018 Mar 1;4 (3):379 - 383.
- Sargent DJ, Shi Q, Yothers G., et al. Prognostic impact of deficient mismatch repair (dMMR) in 7,803 stage II / III colon cancer (CC) patients (pts): A pooled individual pt data analysis of 17 adjuvant trials in the ACCENT database. 10.1200 / jco. 2014.32.15_suppl. 3507 Journal of Clinical Oncology 32, no. 15_suppl (May 20 2014) 3507 - 3507.
- DOI: 10.1200/jco.2014.32.15_suppl.3507JournalofClinicalOncology32
- André T, de Gramont A, Vernerey D, et al. Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study. J Clin Oncol. 2015 Dec 10;33 (35):4176 - 87.
- Pietrantonio F, Raimondi A, Choi YY. MSI-GC-01: Individual patient data (IPD) meta-analysis of microsatellite instability (MSI) and gastric cancer (GC) from four randomized clinical trials (RCTs). 10.1200 / JCO. 2019.37.4_suppl. 66 Journal of Clinical Oncology 37, no. 4_suppl (February 1 2019) 66 - 66.
- DOI: 10.1200/JCO.2019.37.4_suppl.66JournalofClinicalOncology37
- Venderbosch S, Nagtegaal ID, Maughan TS et al. Mismatch repair statusand BRAF mutation status in metastatic colorectal cancer patients: apooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res 2014; 20 (20): 5322 - 5330.
- Taieb J, Shi Q, Pederson L, et al. Prognosis of microsatellite instability and / or mismatch repair deficiency stage III colon cancer patients after disease recurrence following adjuvant treatment: results of an accent pooled analysis of 7 studies. Ann Oncol. 2019 Jul 3. pii: mdz208. 10.1093 / annonc / mdz208. [Epub ahead of print].
- DOI: 10.1093/annonc/mdz208
- Innocenti F, Ou FS, Qu X, et al. Mutational Analysis of Patients With Colorectal Cancer in CALGB / SWOG 80405 Identifies New Roles of Microsatellite Instability and Tumor Mutational Burden for Patient Outcome. J Clin Oncol. 2019 May 10;37 (14):1217 - 1227.
- Diaz-Padilla I, Romero N, Amir E. Mismatch repair status and clinical outcome in endometrial cancer: a systematic review and meta-analysis. Crit Rev Oncol Hematol 2013,88 (1):154 - 167.
- C. L. Creutzberg, A. Leon-Castillo, S. M. de Boer, et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on adjuvant therapy. Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093 / annonc / mdz394.
- DOI: 10.1093/annonc/mdz394
- Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509 - 2520.
- Le DT, Durham JN, Smith KN, et al. Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28; 357 (6349): 409 - 413.
- Le D, Kavan P, Kim T, et al. Safety and antitumor activity of pembrolizumab in patients with advanced microsatellite instability - high (MSI-H) colorectal cancer: KEYNOTE-164. Ann Oncol. 2018;29 (suppl 5):abstr 0 - 021.
- Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair deficient / microsatellite instability - high colorectal cancer (CheckMate 142): results of an open-label, multicentre, phase 2 study. Lancet Oncol. 2017 Sep; 18 (9): 1182 - 1191.
- Overman MJ, Lonardi S, KYM W, et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient / microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36 (8):773 - 9.
- H-J J Lenz, E Van Cutsem, M L Limon, et al. Durable clinical benefit with nivolumab (NIVO) plus low-dose ipilimumab (IPI) as first-line therapy in microsatellite instability-high / mismatch repair deficient (MSI-H / dMMR) metastatic colorectal cancer (mCRC). Ann Oncol, 2018, 29 (8), mdy424.019, https://doi.org / 10.1093 / annonc / mdy424.019.
- DOI: 10.1093/annonc/mdy424.019
- Hochster HS, Bendell JC, Cleary JM et al. Efficacy and safety of atezolizumab (atezo) and bevacizumab (bev) in a phase Ib study of microsatellite nstability (MSI) - high metastatic colorectal cancer (mCRC). Presented at: AmericanSociety of Clinical Oncology Gastrointestinal Cancers Symposium; January 19 - 21, 2017; San Francisco, CA. 2017; abstract 673.
- Eng C, Kim TW, Bendell J, et al. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2019 Jun;20 (6):849 - 861.
- Chalabi M, Fanchi LF, Van den Berg JG, et al. Neoadjuvant ipilimumab plus nivolumab in early stage colon cancer. Ann Oncol. 2018;29 (suppl 8):abstr LBA37.
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Colon Cancer. Version 2.2019. https:// www.nccn.org / professionals / physician_gls / pdf / colon. pdf.
- Kang YK, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390 (10111):2461 - 2471.
- Fuchs CS, Doi T, Jang RW, et al. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol. 2018 May 10;4 (5):e180013.
- Shitara K, Özgüroğlu M, Bang YJ, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392 (10142):123 - 133.
- Tabernero J, Van Cutsem E, Bang Y, et al. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G / GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. J Clin Oncol 2019,37, (suppl; abstr LBA4007).
- Janjigian YY, Bendell J, Calvo E, et al. CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer. J Clin Oncol 2018;36:2836 - 44.
- Kim ST, Cristescu R, Bass AJ, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nature Medicine 2018, 24 (9):1449 - 1458.
- Konstantinopoulos PA, Luo W, Liu JF, et al. Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent / Persistent Endometrial Cancer. J Clin Oncol. 2019 Oct 20;37 (30):2786 - 2794.
- Santin AD, Bellone S, Buza N, et al. Regression of Chemotherapy-Resistant Polymerase (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab. Clin Cancer Res. 2016 Dec 1;22 (23):5682 - 5687.
- Fleming G, Emens L, Eder J, et al. Clinical activity, safety and biomarker results from a phase Ia study of atezolizumab (atezo) in advanced / recurrent endometrial cancer (rEC). J Clin Oncol 2017, 35 (15): 5585 - 5585.
- Makker V., Taylor M. H., Aghajanian C., et al. Lenvatinib (LEN) and Pembrolizumab (PEMBRO) in Advanced Endometrial Cancer (EC). Annals of Oncology (2019) 30 (suppl_5): v403-v434. 10.1093 / annonc / mdz250.
- DOI: 10.1093/annonc/mdz250
- Fukuoka S, Hara H, Takahashi N, et al. Regorafenib plus nivolumab in patients with advanced gastric (GC) or colorectal cancer (CRC): An open-label, dose-finding, and dose-expansion phase 1b trial (REGONIVO, EPOC1603). J Clin Oncol 2019, 37 (15) _suppl: abstr. 2522, 10.1200 / JCO. 2019.37.15_suppl. 2522.
- DOI: 10.1200/JCO.2019.37.15_suppl.2522
- Diaz L. A., Le D., Maio M., et al. Pembrolizumab in microsatellite instability high cancers: updated analysis of the phase 2 KEYNOTE-164 and KEYNOTE-158 studies. Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093 / annonc / mdz253.
- DOI: 10.1093/annonc/mdz253
- Федянин М. Ю., Строгонова А. М., Сендерович А. И., с соавт. Изучение конкордантности мутационного статуса генов KRAS, NRAS, BRAF, PIK3CA между первичной опухолью и метастазами рака толстой кишки. Злокачественные опухоли. 2017; (2):6 - 13.
- Chapusot C, Martin L, Bouvier AM, et al. Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas. Br J Canc 2002;87:400e4.
- Fujiyoshi K, Yamamoto G, Takahashi A, et al. High concordance rate of KRAS / BRAF mutations and MSI-H between primary colorectal cancer and corresponding metastases. Oncol Rep. 2017 Feb;37 (2):785 - 792.
- Sagaert X, Tejpar S, Desmedt L, et al. Intratumoral heterogeneity in colorectal cancer: Can histology be used as a guidance for molecular testing? Journal of Clinical Oncology 35, no. 4_suppl (February 1 2017) 611 - 611.
- Jung J, Kang 1, Lee YJ, Kim E, et al. Comparison of the Mismatch Repair System between Primary and Metastatic Colorectal Cancers Using Immunohistochemistry. J Pathol Transl Med. 2017 Mar;51 (2):129 - 136.
- Cohen R, Hain E, Buhard O, et al. Association of Primary Resistance to Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer With Misdiagnosis of Microsatellite Instability or Mismatch Repair Deficiency Status. JAMA Oncol. 2019 Apr 1;5 (4):551 - 555.
- Yarchoan M, Hopkins A, Jaffee EM. Tumor Mutational Burden and Response Rate to PD-1 Inhibition. N Engl J Med. 2017 Dec 21;377 (25):2500 - 2501.
- Samstein R, Lee CH, Shoushtari A, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nature Genetics, 2019,51:202 - 206.
- Schrock AB, Ouyang C, Sandhu J, et al. Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer. Ann Oncol. 2019 Apr 30. pii: mdz134. 10.1093 / annonc / mdz134.
- DOI: 10.1093/annonc/mdz134
Статья научная
