Иммунорегуляторные функции ингибиторов PD-1/PD-L1 и развитие к ним резистентности
https://doi.org/10.18027/2224-5057-2017-2-94-99
Аннотация
Данный обзор представляет современное понимание об ингибиторах PD-1/PD-L1. Несмотря на выраженный ответ на иммунотерапию ингибиторами чекпоинтов в ряде нозологий, в 60% случаев отмечается либо первичная, либо приобретенная резистентность. Механизмы, лежащие в основе резистентности, также освещены в данной статье.
Об авторе
М. С. СаяпинаРоссия
аспирант отделения клинической фармакологии и химиотерапии
Список литературы
1. Blank C. et al. Blockade of PD-L1 (B7-H1) augments human tumor-specific T cell responses in vitro, Int. J. Cancer, 2006, Vol. 119, No. 2, pp. 317–327.
2. Brahmer J.R., Tykodi S.S., Cho L.Q., Hwu W. J., Topalian S. L., Hwu P. et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer, N. Engl. J. Med. 2012. Vol. 366, pp. 2455–2465.
3. Topalian S. L., Hodi F.S., Brahmer J.R., Gettinger S.N., Smith D.C., McDermott D. F. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer, N. Engl. J. Med. 2012. Vol. 366, pp. 2443–2454.
4. Sharma P., Allison J.P., The future of immune checkpoint therapy, Science, 2015, Vol. 348, No. 6230, pp. 56–61.
5. Okazaki T., Honjo T., PD-1 and PD-1 ligands: from discovery to clinical application, Int. Immunol., 2007, Vol. 19, No. 813–824.
6. Keir M. E., Liang S.C., Guleria I., Latchman Y. E., Qipo A., Albacker L.A. et al. Tissue expression of PD-L1mediates peripheral T cell tolerance, J. Exp. Med., 2006, Vol. 203, No. 4, pp. 883–895.
7. Tseng S.Y., Otsuji M., Gorski K., Huang X., Slansky J. E., Pai S. I. et al. B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells, J. Exp. Med., 2001, Vol. 193, pp. 839–846.
8. Dong H., Strome S. E., Salomao D.R., Tamura H., Hirano F., Flies D.B. et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion, Nat. Med., 2002, Vol. 8, pp. 793–800.
9. Wang L., Pino-Lagos K., de Vries V.C., Guleria I., Sayegh M.H., Noelle R. J., Programmed death 1 ligand signaling regulates the generation of adaptive Foxp3 +CD4+ regulatory T cells, Proc. Natl. Acad.Sci. USA, 2008, Vol. 105, pp. 9331–9336
10. 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, Vol. 99, pp. 12293–12297.
11. Tsushima F., Yao S., Shin T., Flies A., Flies S., Xu H. et al. Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy, Blood, 2007, Vol. 110, pp. 180–185.
12. Ishida Y., Agata Y., Shibahara K., Honjo T. Induced expression of PD1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death, EMBO J., 1992, Vol. 11, pp. 3887–3895.
13. Freeman G. J. et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation, J. Exp. Med., 2000, Vol. 192, pp. 1027–1034.
14. Zitvogel L., Kroemer G., Targeting PD-1/PD-L1 interactions for cancer immunotherapy, OncoImmunology, 2012, Vol. 1:8, pp. 1223–1225.
15. Parry R.V., Chemnitz J.M., Frauwirth K.A., Lanfranco A.R., Braunstein I., Kobayashi S.V. et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms, Mol. Cell. Biol., 2005, Vol. 25, pp. 9543–9553.
16. Marzec M. et al. Oncogenic kinase NPM/ALK induces through STAT3 expression of 573 immunosuppressive protein CD274 (PD-L1, B7-H1), Proc. Natl. Acad.Sci. USA, 2008, Vol. 105, No. 52, pp. 20852–20857.
17. Parsa A. T. et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma, Nat. Med., 2007, Vol. 13, No. 1, pp. 84–88.
18. Mittendorf E.A. et al. PD-L1 expression in triple-negative breast cancer, Cancer Immunol. Res., 2014, Vol. 2, No. 4, pp. 361–370.
19. Ribas A. Adaptive Immune Resistance: How Cancer Protects from Immune Attack, Cancer Discov., 2015, Vol. 5, No. 9, pp. 915–919.
20. Chen L., Han X., Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future, J. Clin. Invest., 2015, Vol. 125, No. 9, pp. 3384–91.
21. Mittal D. et al. New insights into cancer immunoediting and its three component phases elimination, equilibrium and escape, Curr. Opin. Immunol., 2014, Vol. 27, pp. 16–25.
22. Pardoll D.M. The blockade of immune checkpoints in cancer immunotherapy, Nat.Rev. Cancer, 2012, Vol. 12, No. 4, pp. 252–264.
23. Nishimura H., Honjo T., Minato N. Facilitation of beta selection and modification of positive selection in the thymus of PD-1-deficient mice, J. Exp. Med., 2000, Vol. 191, pp. 891–898.
24. Probst H.C., McCoy K., Okazaki T., Honjo T., van den Broek M. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA- 4, Nat. Immunol., 2005, Vol. 6, pp. 280–286.
25. Ansari M. J., Salama A.D., Chitnis T., Smith R.N., Yagita H., Akiba H. et al. The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice, J. Exp. Med., 2003, Vol. 198, pp. 63–69.
26. Francisco L.M., Salinas V.H., Brown K. E., Vanguri V.K., Freeman G. J., Kuchroo V.K. et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells, J. Exp. Med., 2009, Vol. 206, pp. 3015–3029.
27. Dong H., Zhu G., Tamada K., Chen L. B7H1, a third member of the B7 family, co-stimulates Tcell proliferation and interleukin 10 secretion, Nature Med., 1999, Vol. 5, pp. 1365–1369.
28. Latchman Y. et al. PDL2 is a second ligand for PD1 and inhibits T cell activation, Nature Immunol., 2001, Vol. 2, pp. 261–268.
29. Shin T. et al. In vivo costimulatory role of B7DC in tuning T helper cell 1 and cytotoxic T lymphocyte responses, J. Exp. Med., 2005, Vol. 201, pp. 1531–1541.
30. Paterson A.M. et al. The programmed death1 ligand 1: B7–1 pathway restrains diabetogenic effector T cells in vivo, J. Immunol., 2011, Vol. 187, pp. 1097–1105.
31. Park J. J. et al. B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance, Blood, 2010, Vol. 116, pp. 1291–1298.
32. Kuang D.M. et al. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PDL1, J. Exp. Med., 2009, Vol. 206, pp. 1327–1337.
33. Liu Y., Zeng B., Zhang Z., Zhang Y., Yang R. B7H1 on myeloid-derived suppressor cells in immune suppression by a mouse model of ovarian cancer, Clin. Immunol., 2008, Vol. 129, pp. 471–481.
34. Rosenwald A. et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma, J. Exp. Med., 2003, Vol. 198, pp. 851–862.
35. Steidl C. et al. MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers, Nature, 2011, Vol. 471, pp. 377–381.
36. Terme M. et al. IL18 induces PD-1-dependent immunosuppression in cancer, Cancer Res., 2011, Vol. 71, pp. 5393–5399.
37. Fanoni D. et al. New monoclonal antibodies against Bcell antigens: possible new strategies for diagnosis of primary cutaneous Bcell lymphomas, Immunol. Lett., 2011, Vol. 134, pp. 157–160.
38. Velu V. et al. Enhancing SIV-specific immunity in vivo by PD1 blockade, Nature, 2009, Vol. 458, pp. 206–210.
39. Ahmadzadeh M. et al. T cells infiltrating the tumor express high levels of PD1 and are functionally impaired, Blood, 2009, Vol. 114, No. 8, pp. 1537–1544.
40. O’Donnell J.S., Long G.V., Scolyer R.A. et al. Resistance to PD1/PDL1 checkpoint inhibition, Cancer Treatment Reviews, 2017, Vol. 52, pp. 71–81.
41. Schumacher T.N., Schreiber R.D., Neoantigens in cancer immunotherapy, Science, 2015, Vol. 348, No. 6230, pp. 69–74.
42. Martin A.M. et al., Paucity of PD-L1 expression in prostate cancer: innate and adaptive immune resistance, Prostate Cancer Prostatic Dis., 2015, Vol. 18, No. 4, pp. 325–332.
43. Spranger S., Bao R., Gajewski T. F., Melanoma-intrinsic -catenin signaling prevents anti-tumor immunity, Nature, 2015, Vol. 523, No. 7559, pp. 231–235.
44. Ellis L.M., Hicklin D. J. VEGF-targeted therapy: mechanisms of anti- tumor activity, Nat.Rev. Cancer, 2008, Vol. 8, No. 8, pp. 579–591.
45. Young M.R. et al., Tumor-derived cytokines induce bone marrow suppressor cells that mediate immunosuppression through transforming growth factor beta, Cancer Immunol. Immunother., 1992, Vol. 35, No. 1, pp. 14–18.
46. Commeren D. L. et al. Paradoxical effects of interleukin-10 on the maturation of murine myeloid dendritic cells, Immunology, 2003, Vol. 110, No. 2, pp. 188–196.
47. Baas M., Besancon A., Goncalves T. et al. TGFb-dependent expression of PD-1 and PD-L1 controls CD8+ T cell anergy in transplant tolerance eLife 2016; 5: e08133.
48. Thommen D.S. et al., Progression of Lung Cancer Is Associated with Increased Dysfunction of T Cells Defined by Coexpression of Multiple Inhibitory Receptors, Cancer Immunol. Res., 2015, Vol. 3, No. 12, pp. 344–355.
49. Prendergast G.C. Immune escape as a fundamental trait of cancer: focus on IDO, Oncogene, 2008, Vol. 27, pp. 3889–3900.
50. Holmgaard R.B. et al., Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4, J. Exp. Med., 2013, Vol. 210, No. 7, pp. 1389–1402.
51. Spranger S. et al., Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8 (+) T cells 700 directly within the tumor microenvironment, J. Immunother. Cancer, 2014, Vol. 2, p. 3.
52. Zarek P. E. et al. A2A receptor signaling promotes peripheral tolerance by inducing Tcell anergy and the generation of adaptive regulatory T cells, Blood, 2008, Vol. 111, pp. 251–259.
53. Deaglio S. et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression, J. Exp. Med., 2007, Vol. 204, pp. 1257–1265.
54. Ribas A. et al. PD-1 Blockade Expands Intratumoral Memory T Cells, Cancer Immunol. Res., 2016, Vol. 4, No. 3, pp. 194–203.
Рецензия
Для цитирования:
Саяпина М.С. Иммунорегуляторные функции ингибиторов PD-1/PD-L1 и развитие к ним резистентности. Злокачественные опухоли. 2017;(2):94-99. https://doi.org/10.18027/2224-5057-2017-2-94-99
For citation:
Sayapina M.S. Immunoregulatory functions of PD-1/PD-L1 inhibitors and development of resistance to them. Malignant tumours. 2017;(2):94-99. (In Russ.) https://doi.org/10.18027/2224-5057-2017-2-94-99