Visn. Nac. Akad. Nauk Ukr. 2019. (2):44-57 

S.V. Komisarenko, S.I. Romaniuk
Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv

Nobel Prize in Physiology or Medicine for 2018

The Nobel Prize in Physiology and Medicine in 2018 was awarded to two immunologists - James Patrick Allison from the M.D. Anderson Cancer Center at the University of Texas (USA) and Tasuku Honjo from Kyoto University (Japan) for “the discovery of cancer therapy through inhibition of negative immune regulation”. The most prestigious scientific award in 2018 celebrated the implementation of the results of modern immunological research in medical practice, which in recent years has already helped the oncologists successfully fight malignant tumors.

 Language of article: ukrainian



1.     The 2018 Clarivate Citation Laureates.

2.     Press release: The Nobel Prize in Physiology or Medicine 2018.

3.     Global Cancer Observatory, 2018.

4.     From Wikipedia, the free encyclopedia. James P. Allison.

5.     From Wikipedia, the free encyclopedia. Tasuku Honjo.

6.     Gast C.E., Silk A.D., Zarour L., Riegler L., Burkhart J.G., Gustafson K.T., Parappilly M.S., Roh-Johnson M., Goodman J.R., Olson B., Schmidt M., Swain J.R., Davies P.S., Shasthri V., Iizuka S., Flynn P., Watson S., Korkola J., Courtneidge S.A., Fischer J.M., Jaboin J., Billingsley K.G., Lopez C.D., Burchard J., Gray J., Coussens L.M., Sheppard B.C., Wong M.H. Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival. Science Advances. 2018. 4(9): eaat7828.

7.     Busch W. Aus der Sitzung der medizinischen Section vom 18 November 1867. Berliner klinische Wochenschr. 1868. 5: 137.

8.     Coley W.B. Contribution to the knowledge of sarcoma. Ann Surg. 1891. 14(3): 199.

  1. From Wikipedia. Coley's toxins.

10. Lesslauer W., Koning F., Ottenhoff T., Giphart M., Goulmy E., van Rood J.J. T90/44 (9.3 antigen). A cell surface molecule with a function in human T cell activation. Eur. J. Immunol. 1986. 16(10): 1289.

11. López de Castro J.A., Orr H.T., Robb R.J., Kostyk T.G., Mann D.L., Strominger J.L. Complete amino acid sequence of a papain-solubilized human histocompatibility antigen HLA-B7. 1. Isolation and amino acid composition of fragments and of tryptic and chymotryptic peptides. Biochemistry. 1979. 18(25): 5704.

12. Brunet J.F., Denizot F., Luciani M.F., Roux-Dosseto M., Suzan M., Mattei M.G., Golstein P. A new member of the immunoglobulin superfamily – CTLA-4. Nature. 1987. 328(6127): 267.

13. Krummel M.F., Allison J.P. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J. Exp. Med. 1995. 182(2): 459 .

14. Harper K., Balzano C., Rouvier E., Mattéi M.G., Luciani M.F., Golstein P. CTLA-4 and CD28 activated lymphocyte molecules are closely related in both mouse and human as to sequence, message expression, gene structure, and chromosomal location. J. Immunol. 1991. 147(3): 1037.

15. Egen J.G., Allison J.P. Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity. 2002. 16(1): 23.

16. Ganesan A., Moon T.C., Barakat K.H. Revealing the atomistic details behind the binding of B7-1 to CD28 and CTLA-4: A comprehensive protein-protein modelling study. Biochim. Biophys. Acta Gen. Subj. 2018. 1862(12): 2764.

17. Ishida Y., Agata Y., Shibahara K., Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992. 11(11): 3887.

18. Nishimura H., Okazaki T., Tanaka Y., Nakatani K., Hara M., Matsumori A., Sasayama S., Mizoguchi A., Hiai H., Minato N., Honjo T. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001. 291(5502): 319.

19. Freeman G.J., Long A.J., Iwai Y., Bourque K., Chernova T., Nishimura H., Fitz L.J., Malenkovich N., Okazaki T., Byrne M.C., Horton H.F., Fouser L., Carter L., Ling V., Bowman M.R., Carreno B.M., Collins M., Wood C.R., Honjo T. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 2000. 192(7): 1027.

20. Latchman Y., Wood C.R., Chernova T., Chaudhary D., Borde M., Chernova I., Iwai Y., Long A.J., Brown J.A., Nunes R., Greenfield E.A., Bourque K., Boussiotis V.A., Carter L.L., Carreno B.M., Malenkovich N., Nishimura H., Okazaki T., Honjo T., Sharpe A.H., Freeman G.J. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat. Immunol. 2001. 2(3): 261.

21. Zhang X., Schwartz J.C., Guo X., Bhatia S., Cao E., Lorenz M., Cammer M., Chen L., Zhang Z.Y., Edidin M.A., Nathenson S.G., Almo S.C. Structural and functional analysis of the costimulatory receptor programmed death-1. Immunity. 2004. 20(3): 337.

22. Iwai Y., Ishida M., Tanaka Y., Okazaki T., Honjo T., Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc. Natl. Acad. Sci. USA. 2002. 99(19): 12293.

23. Dong H., Strome S.E., Salomao D.R., Tamura H., Hirano F., Flies D.B., Roche P.C., Lu J., Zhu G., Tamada K., Lennon V.A., Celis E., Chen L. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 2002. 8(8): 793.

24. Lenschow D.J., Zeng Y., Thistlethwaite J.R., Montag A., Brady W., Gibson M.G., Linsley P.S., Bluestone J.A. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg. Science. 1992. 257(5071): 789.

25. Leach D.R., Krummel M.F., Allison J.P. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996. 271(5256): 1734.

26. Iwai Y., Terawaki S., Honjo T. PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int. Immunol. 2005. 17(2): 133.

27. Hirano F., Kaneko K., Tamura H., Dong H., Wang S., Ichikawa M., Rietz C., Flies D.B., Lau J.S., Zhu G., Tamada K., Chen L. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res. 2005. 65(3): 1089.

28. Wolchok J.D., Hodi F.S., Weber J.S., Allison J.P., Urba W.J., Robert C., O'Day S.J., Hoos A., Humphrey R., Berman D.M., Lonberg N., Korman A.J. Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma. Ann. NY Acad. Sci. 2013. 1291: 1.

29. Topalian S.L., Hodi F.S., Brahmer J.R., Gettinger S.N., Smith D.C., McDermott D.F., Powderly J.D., Carvajal R.D., Sosman J.A., Atkins M.B., Leming P.D., Spigel D.R., Antonia S.J, Horn L., Drake C.G., Pardoll D.M., Chen L., Sharfman W.H., Anders R.A., Taube J.M., McMiller T.L., Xu H., Korman A.J., Jure-Kunkel M., Agrawal S., McDonald D., Kollia G.D., Gupta A., Wigginton J.M., Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 2012. 366(26): 2443. 10.1056/NEJMoa1200690

30. Weber J., Mandala M., Del Vecchio M., Gogas H.J., Arance A.M., Cowey C.L., Dalle S., Schenker M., Chiarion-Sileni V., Marquez-Rodas I., Grob J.J., Butler M.O., Middleton M.R., Maio M., Atkinson V., Queirolo P., Gonzalez R., Kudchadkar R.R., Smylie M., Meyer N., Mortier L., Atkins M.B., Long G.V., Bhatia S., Lebbé C., Rutkowski P., Yokota K., Yamazaki N., Kim T.M., de Pril V., Sabater J., Qureshi A., Larkin J., Ascierto P.A.; CheckMate 238 Collaborators. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N. Engl. J. Med. 2017. 377(19): 1824.

31. Wolchok J.D., Chiarion-Sileni V., Gonzalez R., Rutkowski P., Grob J.J., Cowey C.L., Lao C.D., Wagstaff J., Schadendorf D., Ferrucci P.F., Smylie M., Dummer R., Hill A., Hogg D., Haanen J., Carlino M.S., Bechter O., Maio M., Marquez-Rodas I., Guidoboni M., McArthur G., Lebbé C., Ascierto P.A., Long G.V., Cebon J., Sosman J., Postow M.A., Callahan M.K., Walker D., Rollin L., Bhore R., Hodi F.S., Larkin J. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N. Engl. J. Med. 2017. 377(14): 1345.

32. USA former president Carter recovered from brain cancer.

33. Eggermont A.M.M., Robert C., Ribas A. The new era of adjuvant therapies for melanoma. Nat. Rev. Clin. Oncol. 2018. 15(9): 535.

34. Ansell S.M., Lesokhin A.M., Borrello I., Halwani A., Scott E.C., Gutierrez M., Schuster S.J., Millenson M.M., Cattry D., Freeman G.J., Rodig S.J., Chapuy B., Ligon A.H., Zhu L., Grosso J.F., Kim S.Y., Timmerman J.M., Shipp M.A., Armand P. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N. Engl. J. Med. 2015. 372(4): 311.

35. Rizvi N.A., Hellmann M.D., Snyder A., Kvistborg P., Makarov V., Havel J.J., Lee W., Yuan J., Wong P., Ho T.S., Miller M.L., Rekhtman N., Moreira A.L., Ibrahim F., Bruggeman C., Gasmi B., Zappasodi R., Maeda Y., Sander C., Garon E.B., Merghoub T., Wolchok J.D., Schumacher T.N., Chan T.A. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015. 348(6230): 124.

36. Chowell D., Morris L.G.T., Grigg C.M., Weber J.K., Samstein R.M., Makarov V., Kuo F., Kendall S.M., Requena D., Riaz N., Greenbaum B., Carroll J., Garon E., Hyman D.M., Zehir A., Solit D., Berger M., Zhou R., Rizvi N.A., Chan T.A. Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science. 2018. 359(6375): 582.

37. Routy B., Le Chatelier E., Derosa L., Duong C.P.M., Alou M.T., Daillère R., Fluckiger A., Messaoudene M., Rauber C., Roberti M.P., Fidelle M., Flament C., Poirier-Colame V., Opolon P., Klein C., Iribarren K., Mondragón L., Jacquelot N., Qu B., Ferrere G., Clémenson C., Mezquita L., Masip J.R., Naltet C., Brosseau S., Kaderbhai C., Richard C., Rizvi H., Levenez F., Galleron N., Quinquis B., Pons N., Ryffel B., Minard-Colin V., Gonin P., Soria J.C., Deutsch E., Loriot Y., Ghiringhelli F., Zalcman G., Goldwasser F., Escudier B., Hellmann M.D., Eggermont A., Raoult D., Albiges L., Kroemer G., Zitvogel L. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018. 359(6371): 91.

38. Mariathasan S., Turley S.J., Nickles D., Castiglioni A., Yuen K., Wang Y., Kadel E.E. III, Koeppen H., Astarita J.L., Cubas R., Jhunjhunwala S., Banchereau R., Yang Y., Guan Y., Chalouni C., Ziai J., Şenbabaoğlu Y., Santoro S., Sheinson D., Hung J., Giltnane J.M., Pierce A.A., Mesh K., Lianoglou S., Riegler J., Carano R.A.D., Eriksson P., Höglund M., Somarriba L., Halligan D.L., van der Heijden M.S., Loriot Y., Rosenberg J.E., Fong L., Mellman I., Chen D.S., Green M., Derleth C., Fine G.D., Hegde P.S., Bourgon R., Powles T. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018. 554(7693): 544.

39. Postow M.A., Sidlow R., Hellmann M.D. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N. Engl. J. Med. 2018. 378(2): 158.

40. Liskovych M. Nobel Prize in Medicine is a forward step in immunotherapy of cancer. Rather costly yet...]

41. Fang F., Xiao W., Tian Z. NK cell-based immunotherapy for cancer. Semin. Immunol. 2017. 31: 37.

42. Mulcahy N. FDA Approves provenge, the first immunotherapy for metastatic prostate cancer.

  1. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine. Anticancer autovaccinum..

44. Kranz L.M., Diken M., Haas H., Kreiter S., Loquai C., Reuter K.C., Meng M., Fritz D., Vascotto F., Hefesha H., Grunwitz C., Vormehr M., Hüsemann Y., Selmi A., Kuhn A.N., Buck J., Derhovanessian E., Rae R., Attig S., Diekmann J., Jabulowsky R.A., Heesch S., Hassel J., Langguth P., Grabbe S., Huber C., Türeci Ö., Sahin U. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature. 2016. 534(7607): 396.

45. Oleinik E.S., Labyntsev A.Yu., Manoylov K.Yu., Kolibo D.V., Komisarenko S.V. Immunoliposomes for the targeted delivery of biologically active compounds into the cells of tumor tissues. In: Nano-Sized Systems and Nanomaterials: Research in Ukraine. (Kyiv: Akademperiodyka, 2014). P. 510–514.

46. Zaroff S. CAR T-Cell Therapies with a Bispecific Twist. Tutorials. 2018. 38(13)).

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