Preview

Злокачественные опухоли

Расширенный поиск

Современные иммунологические биомаркеры рака толстой кишки

https://doi.org/10.18027/2224-5057-2018-8-4-50-58

Полный текст:

Аннотация

В статье кратко описан механизм действия иммунотерапевтических препаратов, подавляющих активность «чекпоинтов» иммунного ответа CTLA-4 и PD-1. Приведены современные данные о клинической эффективности и преимуществах применения ниволумаба, пембролизумаба и атезолизумаба при колоректальном раке. Обобщена существующая доказательная база о потенциальной предиктивной и прогностической роли MSI-статуса и представлена информация о перспективах дальнейшего развития данного метода лекарственного лечения злокачественных опухолей.

Об авторах

А. А. Трякин
ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина»
Россия
д. м. н., с. н. с. отделения клинической фармакологии и химиотерапии


Г. Г. Хакимова
ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина»
Россия
аспирант отделения химиотерапии и комбинированного лечения злокачественных опухолей


Т. Н. Заботина
ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина»
Россия
д. б. н., зав. централизованным клинико-лабораторным отделом


А. А. Борунова
ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина»
Россия
к. м. н., с. н. с. лаборатории клинической иммунологии опухолей


О. А. Малихова
ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина»
Россия
д. м. н., проф., зав. отделения эндоскопического


Список литературы

1. Pernot, Simon et al. “Colorectal Cancer and Immunity: What We Know and Perspectives.” World Journal of Gastroenterology: WJG. 2014. P. 3738–3750. PMC. Web. 2 July 2018.

2. Состояние онкологической помощи населению России в 2016 году / под ред. Каприна А. Д., Старинского В. В., Петровой Г. В. М., 2017. 236 с.

3. Pernot S., Terme M., Voron T. et al. Colorectal cancer and immunity: What we know and perspectives. World Journal of Gastroenterology: WJG. 2014. Vol. 20(14). P. 3738–3750. DOI: 10.3748/wjg.v20.i14.3738.

4. Bilgin B., Sendur M.A., Bulent Akinci M., Sener Dede D., Yalсin B. Targeting PD-1 Pathway: A new hope for Gastrointestinal Cancers. Current Medical Research and Opinion. 2017. Vol. 33(4). P. 749–759. DOI: 10.1080/03007995.2017.1279132.

5. Hewish M., Lord C.J., Martin S.A. et al. Mismatch repair deficient colorectal cancer in the era of personalized treatment. Nat. Rev. Clin. Oncol. 2010. Vol. 7. P. 197–208.

6. Gatalica Z., Vranic S., Xiu J. et al. High microsatellite instability (MSI-H) colorectal carcinoma: a brief review of predictive biomarkers in the era of personalized medicine. Fam Cancer. 2016. Vol. 15. P. 405–412. DOI: 10.1007/s10689-016-9884-6.

7. Modrich P. Mechanisms in eukaryotic mismatch repair. J. Biol. Chem. 2006. Vol. 281. P. 30305-9. DOI: 10.1074/jbc.R600022200.

8. Jiricny J. The multifaceted mismatch-repair system. Nat. Rev. Mol. Cell Biol. 2006. Vol. 7. P. 335–346.

9. Li G.M. Mechanisms and functions of DNA mismatch repair. Cell Res. 2008. Vol. 18. P. 85–98.

10. Devaud N., Gallinger S. Chemotherapy of MMR-deficient colorectal cancer. Fam Cancer. 2013. Vol. 12. P. 301–306. DOI: 10.1007/s10689-013-9633-z.

11. Smyrk T.C., Watson P., Kaul K. et al. Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma. Cancer. 2001. Vol. 91. P. 2417–2422. DOI: 10.1002/1097-0142(20010615)91:12<2417::AID-CNCR1276>3.0.CO;2-U.

12. Benatti P., Gafa R., Barana D., Marino M., Scarselli A., Pedroni M., Maestri I., Guerzoni L. et al. Microsatellite instability and colorectal cancer prognosis. Clin. Cancer Res. 2005. Vol. 11. P. 8332–8340.

13. Zaanan A., Shi Q., Taieb J. et al. Analysis of DNA mismatch repair (MMR) and clinical outcome in stage III colon cancers from patients (pts) treated with adjuvant FOLFOX +/– cetuximab in the PETACC8 and NCCTG N0147 adjuvant trials. J. Clin. Oncol. 2015. Vol. 33. P. 3506.

14. Popat S., Hubner R., Houlston R.S. Systematic review of microsatellite instability and colorectal cancer prognosis. 2005. J. Clin. Oncol. Vol. 23. P. 609–618.

15. Barratt P.L., Seymour M.T., Stenning S.P. et al. Adjuvant x-ray and fluorouracil infusion study: DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer — A molecular study. Lancet. 2002. Vol. 360. P. 1381–1391.

16. Zaanan A., Shi Q., Taieb J. et al. Analysis of DNA mismatch repair (MMR) and clinical outcome in stage III colon cancers from patients (pts) treated with adjuvant FOLFOX +/– cetuximab in the PETACC8 and NCCTG N0147 adjuvant trials. J. Clin. Oncol. 2015. Vol. 33. P. 3506.

17. Tougeron D., Mouillet G., Trouilloud I. et al. Efficacy of adjuvant chemotherapy in colon cancer with microsatellite instability: a large multicenter AGEO study. J. Natl. Cancer Inst. 2016. Vol. 108(7). DOI: 10.1093/jnci/djv438.

18. Mellman I., Coukos G., Dranoff G. Cancer immunotherapy comes of age. Nature. 2011. Vol. 480. P. 480–489.

19. Dizon D.S., Krilov L., Cohen E., Gangadhar T., Ganz P.A., Hensing T.A., Hunger S. et al. Clinical Cancer Advances 2016: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology. J. Clin. Oncol. 2016. Vol. 34. No. 9. P. 987–1011.

20. Jacobs J., Smits E., Lardon F., Pauwels P., Deschoolmeester V. Immune Checkpoint Modulation in Colorectal Cancer: What’s New and What to Expect. Journal of immunology research. 2015. Vol. 2015. P. 58038.

21. Reiss K.A., Forde P.M., Brahmer J.R. Harnessing the power of the immune system via blockade of PD-1 and PD-L1: a promising new anticancer strategy. Immunotherapy. 2014. Vol. 6(4). P. 459–75.

22. Patel S.P., Kurzrock R. PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy. Mol. Cancer Ther. 2015. Vol. 14. P. 847–56.

23. Blackburn S.D., Shin H., Haining W.N. et al. Coregulation of CD8. T cell exhaustion by multiple inhibitory receptors during chronic viral infection. NatImmunol. 2009. Vol. 10(1). P. 29–37.

24. 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. Vol. 5. P. 43–51.

25. Brahmer J.R., Tykodi S.S., Chow L.Q. et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 2012. Vol. 366. P. 2455–65.

26. Topalian S.L., Hodi F.S., Brahmer J.R. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 2012. Vol. 366. P. 2443–54.

27. Le D.T., Uram J.N., Wang H. et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N. Engl. J. Med. 2015. Vol. 372. P. 2509–20.

28. Le D.T., Durham J.N., Smith K.N. et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017. Vol. 357. P. 409–413.

29. Le D.T., Uram J.N., Wang H., Bartlett B.R., Kemberling H., Eyring A.D. et al. PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med. 2015. Vol. 372(26). P. 2509–20. https://doi.org/10.1056/NEJMoa1500596.

30. Diaz L.A., Marabelle A., Delord J.P. et al. Pembrolizumab therapy for microsatellite instability high (MSI-H) colorectal cancer (CRC) and non-CRC. J. Clin. Oncol. 2017. Vol. 35. P. 3071.

31. Lemery S., Keegan P., Pazdur R. First FDA Approval Agnostic of Cancer Site – When a Biomarker De nes the Indication. N. Engl. J. Med. 2017. Vol. 377. P. 1409–12.

32. Overman M.J., McDermott R., Leach J.L. et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017. Vol. 18. P. 1182–91.

33. Overman M.J., Bergamo F., Mcdermott R.S. et al. Nivolumab in patients with DNA mismatch repair- deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC): long-term survival according to prior line of treatment from CheckMate-142. J. Clin. Oncol. 2018. Vol. 36. abstr 554.

34. FDA grants nivolumab accelerated approval for MSI-H or dMMR colorectal cancer. Available online: www. fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm569366.htm.

35. Shia J. Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. J. Mol. Diagn. 2008. Vol. 10. P. 293–300.

36. Shia J., Stadler Z., Weiser M.R. et al. Immunohistochemical staining for DNA mismatch repair proteins in intestinal tract carcinoma: how reliable are biopsy samples? Am. J. Surg. Pathol. 2011. Vol. 35. P. 447–454.

37. Chu F., Neelapu S.S. Anti-PD-1 antibodies for the treatment of B-celllymphoma: Importance of PD-1+ T-cell subsets. Oncoimmunology. 2014. Vol. 3(1). P. e28101. DOI: 10.4161/onci.28101.

38. Pardoll D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer. 2012. Vol. 12. No. 4. P. 252–264.

39. Overman M.J., Lonardi S., Wong K.Y.M. et al. Durable Clinical Benet With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J. Clin. Oncol. 2018. Vol. 36. P. 773–779.

40. Hochster H.S., Bendell J.C., Cleary J.M. et al. Efficacy and safety of atezolizumab (atezo) and bevacizumab (bev) in a phase Ib study of microsatellite instability (MSI) – high metastatic colorectal cancer (mCRC). J. Clin. Oncol. 2017. Vol. 35. P. 673.

41. Bendell J.C., Powderly J.D., Lieu C.H. et al. Safety and efficacy of MPDL3280A (anti-PDL1) in combination with bevacizumab (bev) and/or FOLFOX in patients (pts) with metastatic colorectal cancer (mCRC). J. Clin. Oncol. 2015. Vol. 33. P. 704.

42. Duffy A.G., Makarova-Rusher O.V., Fioravanti S. et al. A pilot study of AMP-224, a PD-L2 Fc fusion protein, in combination with stereotactic body radiation therapy (SBRT) in patients with metastatic colorectal cancer. J. Clin. Oncol. 2016. Vol. 34. P. 560.

43. Dhillon A.S., Hagan S., Rath O. et al. MAP kinase signalling pathways in cancer. Oncogene. 2007. Vol. 26. P. 3279–90.

44. Ebert P.J.R., Cheung J., Yang Y. et al. MAP Kinase Inhibition Promotes T Cell and Anti-tumor Activity in Combination with PD-L1 Checkpoint Blockade. Immunity. 2016. Vol. 44. P. 609–621.

45. Bendell J.C., Kim T.W., Goh B.C. et al. Clinical activity and safety of cobimetinib (cobi) and atezolizumab in colorectal cancer (CRC). J. Clin. Oncol. 2016. Vol. 34. P. 3502.

46. Bendell J., Ciardiello F., Tabernero J. et al. Efficacy and safety results from IMblaze370, a randomised Phase III study comparing atezolizumab+cobimetinib and atezolizumab monotherapy vs regorafenib in chemotherapy-refractory metastatic colorectal cancer. Annals of Oncology. 2018. Vol. 29. Issue suppl_5. https://doi.org/10.1093/annonc/mdy208.003.

47. Bacac M., Fauti T., Sam J. et al. A Novel Carcinoembryonic Antigen T-Cell Bispeci c Antibody (CEA TCB) for the Treatment of Solid Tumors. Clin. Cancer Res. 2016. Vol. 22. P. 3286–97.

48. Tiernan J.P., Perry S.L., Verghese E.T. et al. Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting. Br. J. Cancer. 2013. Vol. 108. P. 662–667.

49. Lehmann S., Perera R., Grimm H.P. et al. In Vivo Fluorescence Imaging of the Activity of CEA TCB, a Novel T-Cell Bispeci c Antibody, Reveals Highly Speci c Tumor Targeting and Fast Induction of T-Cell-Mediated Tumor Killing. Clin. Cancer Res. 2016. Vol. 22. P. 4417–27.

50. Tabernero J., Melero I., Ros W. et al. Phase Ia and Ib studies of the novel carcinoembryonic antigen (CEA) T-cell bispeci c (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab: Preliminary ef cacy and safety in patients with metastatic colorectal cancer (mCRC). J. Clin. Oncol. 2017. Vol. 35. P. 3002.

51. Carbognin L., Pilotto S., Milella M. et al. Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers. PLoS One. 2015. Vol. 10. e0130142.

52. O’Neil B.H., Wallmark J., Lorente D. et al. Pembrolizumab (MK-3475) for patients (pts) with advanced colorectal carcinoma (CRC): Preliminary results from KEYNOTE-028. Eur. J. Cancer. 2015. Vol. 51. abstr s103.

53. Overman M.J., McDermott R., Leach J.L. et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017. Vol. 18. P. 1182–91.


Для цитирования:


Трякин А.А., Хакимова Г.Г., Заботина Т.Н., Борунова А.А., Малихова О.А. Современные иммунологические биомаркеры рака толстой кишки. Злокачественные опухоли. 2018;8(4):50-58. https://doi.org/10.18027/2224-5057-2018-8-4-50-58

For citation:


Tryakin A.A., Khakimova G.G., Zabotina T.N., Borunova A.A., Malikhova O.A. Modern views on immunological biomarkers of colon cancer. Malignant tumours. 2018;8(4):50-58. (In Russ.) https://doi.org/10.18027/2224-5057-2018-8-4-50-58

Просмотров: 154


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 2224-5057 (Print)
ISSN 2587-6813 (Online)