350 rub
Journal Technologies of Living Systems №1 for 2021 г.
Article in number:
Key immune checkpoints and their inhibitors in the therapy of bone tumors. Part 1. Signaling system of programmed cell death protein 1 - PD-1/PD-L
DOI: 10.18127/j20700997-202101-01
UDC: 616.71-006-085:612.017.1
Keywords: Bone tumors PD-1 PD-L1 sPD-1 sPD-L1 immunotherapy.
Authors:

A.A. Alferov¹, M.M. Efimova², Yu.B. Kuzmin³, I.N. Kuznetsov4, E.S. Gershtein5, N.E. Kushlinskii6

1–3, 5, 6 N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation  (Moscow, Russia)

4 A.I. Evdokimov Moscow University of Medicine and Dentistry of the Ministry of Health of the Russian Federation (Moscow, Russia)

Abstract:

The intent interest of oncologists in bone sarcomas is imposed by the prevalence of these diseases at advanced stages in children, adolescent and young people, its aggressiveness, resistance to chemotherapy, and unfavorable prognosis. Currently, attempts to affect these diseases by blockers of one of the key immune checkpoints PD-1/PD-L taking into consideration programmed cell death 1 receptor protein and its ligand PD-L1 expression in the tumor, or the content of their soluble forms sPD-1 and sPD-L1 in blood serum of primary bone tumor patients are performed.

Aim of the work – analysis of the clinical implications of the investigation of PD-1 and PD-L1 expression in the tumors and the content of sPD-1 and sPD-L1 in blood serum of patients with the most common malignant bone tumors.

The investigations of PD-1/PD-L1 expression and their soluble forms circulation in bone sarcoma patients are presented in a limited number of publications. The PD-L1 ligand expression was found in experimental studies with osteosarcoma (OS) cell lines and in human OS samples. The levels of PD-L1 expression in OS cell lines widely varied, the expression in drug-resistant lines being higher than in corresponding parental lines. Meta-analysis of 14 OS studies demonstrated 14–75% increased PD-L1 expression in the tumors as compared to adjacent tissues, that significantly correlated with metastasizing, high mortality risk and low overall survival. PD-L1 expression with various staining intensity was revealed in 39% of Ewing sarcomas (EwS), 67.5% chondrosarcomas (ChS) and 94.5% chordomas. In OS patients, statistically significant correlation between increased PD-L1 expression on tumor cells and the number of TILs was found. The first results of sPD-1 and sPD-L1 determination in blood serum of patients with different bone neoplasms are demonstrated: sPD-L1 levels in OS, ChS, EwS, chordoma, giant-cell and benign bone tumor patients were statistically significantly higher than in control healthy persons. Results of the first clinical trials of anti-PD-1/PD-L drugs in bone sarcoma patients are described.

The level of tumor PD-1 and PD-L1 expression and sPD-1 and sPD-L1 level in blood serum of bone sarcoma patients correlate with certain clinical and morphological characteristics and can be regarded as useful markers for the monitoring of anti- PD1/PD-L1 treatment efficiency and the prognosis of patients’ survival. The problem, however, requires further investigation.

Pages: 5-17
For citation

Alferov A.A., Efimova M.M., Kuzmin Yu.B., Kuznetsov I.N., Gershtein E.S., Kushlinskii N.E. Key immune checkpoints and their inhibitors in the therapy of bone tumors. Part 1. Signaling system of programmed cell death protein 1 – PD-1/PD-L. Technologies of living systems. 2021. V. 18. № 1. P. 5–17. DOI: 10.18127/j20700997-202101-01 (In Russian).

References
  1. Group ESESNW. Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2014. V. 25. Suppl. 3. P. 113–123.
  2. Casali P.G., Abecassis N., Bauer S. et al. Soft tissue and visceral sarcomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2018. V. 29. Suppl 4. P. 51–67.
  3. Unni K.K., Inwards C.Y. Dahlin’s bone tumors: general aspects and data on 10165 cases – Philadelphia: Lippincott Williams & Wilkins. 2006.
  4. de Alava E.L.S., Sorensen P.H. Chapter 19: Ewing sarcoma. In: Fletcher C.D.M. B.J., Hogendoorn P.C.W., Mertens F., editors. WHO Classification of Tumours of Soft Tissue and Bone. Lyon: IARC; 2013.
  5. Maeda N., Yoshimura K., Yamamoto S. et al. Expression of B7-H3, a potential factor of tumor immune evasion in combination with the number of regulatory T cells, affects against recurrence-free survival in breast cancer patients. Ann. Surg. Oncol. 2014. V. 21. Suppl. 4. P. 546–555.
  6. Kang F.B., Wang L., Jia H.C. et al. B7-H3 promotes aggression and invasion of hepatocellular carcinoma by targeting epithelial-tomesenchymal transition via JAK2/STAT3/Slug signaling pathway. Cancer Cell Int. 2015. № 15. P. 45.
  7. Chavin G., Sheinin Y., Crispen P.L. et al. Expression of immunosuppresive B7-H3 ligand by hormone-treated prostate cancer tumors and metastases. Clin. Cancer Res. 2009. V. 15. P. 2174–2180.
  8. Fernández L., Metais J.Y., Escudero A., Vela M., Valentín J., Vallcorba I., Leivas A., Torres J., Valeri A., Patiño-García A., Martínez J., Leung W., Pérez-Martínez A. Memory T cells expressing an NKG2D-CAR efficiently target osteosarcoma cells. Clin. Cancer Res. 2017. V. 23. № 19. P. 5824–5835.
  9. McEachron T.A., Triche T.J., Sorenson L., Parham D.M., Carpten J.D. Profiling targetable immune checkpoints in osteosarcoma. Oncoimmunology. 2018. V. 7. № 12. e1475873.
  10. Wang L., Zhang Q., Chen W. et al. B7-H3 is overexpressed in patients suffering osteosarcoma and associated with tumor aggressiveness and metastasis. PLoS One. 2013. V. 8. Article e70689.
  11. Kyi C., Postow M.A. Checkpoint blocking antibodies in cancer immunotherapy. FEBS Lett. 2014. V. 588. № 2. P. 368–376.
  12. Tsukahara T., Emori M., Murata K., Mizushima E., Shibayama Y., Kubo T., Kanaseki T., Hirohashi Y., Yamashita T., Sato N., Torigoe T. The future of immunotherapy for sarcoma. Expert. Opin. Biol. Ther. 2016. V. 16. № 8. P. 1049–1057.
  13. Kabir T.F., Chauhan A., Anthony L., Hildebrandt G.C. Immune Checkpoint Inhibitors in Pediatric Solid Tumors: Status in 2018. Ochsner J. 2018 Winter. V. 18. № 4. P. 370–376.
  14. Huang H.F., Zhu H., Yang X.T., Guo X.Y., Li S.S., Xie Q., Tian X.B., Yang Z. Progress in Research on Tumor Immune PD-1/PD-L1 Signaling Pathway in Malignant Bone Tumors. Zhonghua Zhong Liu Za Zhi. 2019. V. 41. № 6. P. 410–414.
  15. Sakamoto A., Iwamoto Y. Current status and perspectives regarding the treatment of osteosarcoma: chemotherapy. Rev. Recent. Clin. Trials. 2008. V. 3. № 3. P. 228–231.
  16. Stiefel F., Barth J., Bensing J., Fallowfield L., Jost L., Razavi D., Kiss A.; participants. Communication skills training in oncology: a position paper based on a consensus meeting among European experts in 2009. Ann. Oncol. 2010. V. 21. № 2. P. 204–207.
  17. Wachtel M., Schäfer B.W. Targets for cancer therapy in childhood sarcomas. Cancer Treat. Rev. 2010. V. 36. № 4. P. 318–327.
  18. Raj S., Bui M., Gonzales R., Letson D., Antonia S.J. Impact of PDL1 expression on clinical outcomes in subtypes of sarcoma. Ann. Oncol. 2014. V. 25. P. 494–510.
  19. Shen J.K., Cote G.M., Choy E., Yang P., Harmon D., Schwab J., Nielsen G.P., Chebib I., Ferrone S., Wang X., Wang Y., Mankin H., Hornicek F.J., Duan Z. Programmed cell death ligand 1 expression in osteosarcoma. Cancer Immunol. Res. 2014. V. 2. № 7. P. 690–698.
  20. Chowdhury F., Dunn S., Mitchell S., Mellows T., Ashton-Key M., Gray J.C. PD-L1 and CD8+PD1+ lymphocytes exist as targets in the pediatric tumor microenvironment for immunomodulatory therapy. OncoImmunology. 2015. V. 4. № 10. Article e1029701.
  21. Koirala P., Roth M.E., Gill J., Piperdi S., Chinai J.M., Geller D.S., Hoang B.H., Park A., Fremed M.A., Zang X., Gorlick R. Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma. Sci. Rep. 2016. V. 6. P. 30093.
  22. Lussier D.M., O'Neill L., Nieves L.M., McAfee M.S., Holechek S.A., Collins A.W., Dickman P., Jacobsen J., Hingorani P., Blattman J.N. Enhanced T-cell immunity to osteosarcoma through antibody blockade of PD-1/PD-L1 interactions. J. Immunother. 2015. V. 38. № 3. P. 96–106.
  23. Costa Arantes D.A., Goncalves A.S., Jham B.C., Duarte E.C.B., de Paula E.C., de Paula H.M., Mendonca E.F., Batista A.C. Evaluation of HLA-G, HLA-E, and PD-L1 proteins in oral osteosarcomas. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2017. V. 123. № 6. P.188–196.
  24. Liao Y., Chen L., Feng Y., Shen J., Gao Y., Cote G., Choy E., Harmon D., Mankin H., Hornicek F., Duan Z. Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells. Oncotarget. 2017. V. 8. № 18. P. 30276–30287.
  25. Zhu Z., Jin Z., Zhang M., Tang Y., Yang G., Yuan X., Yao J., Sun D. Prognostic value of programmed death-ligand 1 in sarcoma: a meta-analysis. Oncotarget. 2017. V. 8. № 35. P. 59570–59580.
  26. Dhupkar P., Gordon N., Stewart J., Kleinerman E.S. Anti-PD-1 therapy redirects macrophages from an M2 to an M1 phenotype inducing regression of OS lung metastases. Cancer Med. 2018. V. 7. № 6. P. 2654–2664.
  27. Shimizu T., Fuchimoto Y., Fukuda K., Okita H., Kitagawa Y., Kuroda T. The effect of immune checkpoint inhibitors on lung metastases of osteosarcoma. J. Pediatr. Surg. 2017. V. 52. № 12. P. 2047–2050.
  28. Zheng B., Ren T., Huang Y., Sun K., Wang S., Bao X., Liu K., Guo W. PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse. J. Hematol. Oncol. 2018. V. 11. № 1. P. 16.
  29. Tawbi H.A., Burgess M., Bolejack V., Van Tine B.A., Schuetze S.M., Hu J., D'Angelo S., Attia S., Riedel R.F., Priebat D.A., Movva S., Davis L.E., Okuno S.H., Reed D.R., Crowley J., Butterfield L.H., Salazar R., Rodriguez-Canales J., Lazar A.J., Wistuba I.I., Baker L.H., Maki R.G., Reinke D., Patel S. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, twocohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017. V. 18. № 11. P. 1493–1501.
  30. Gurney G.J. SA, Bulterys M. Malignant bone tumours. Bethesda, MD: National Cancer Institute, SEER Program; 1999.
  31. McCaughan G.J., Fulham M.J., Mahar A., Soper J., Hong A.M., Stalley P.D., Tattersall M.H., Bhadri V.A. Programmed cell death-1 blockade in recurrent disseminated Ewing sarcoma. J. Hematol. Oncol. 2016. V. 9. № 1. P. 48.
  32. Grünewald T.G.P., Cidre-Aranaz F., Surdez D., Tomazou E.M., de Álava E., Kovar H., Sorensen P.H., Delattre O., Dirksen U. Ewing sarcoma. Nat. Rev. Dis. Primers. 2018. V. 4. № 1. P. 5.
  33. Gaspar N., Hawkins D.S., Dirksen U. et al. Ian J Lewis 1, Stefano Ferrari 1, Marie-Cecile Le Deley 1, Heinrich Kovar 1, Robert Grimer 1, Jeremy Whelan 1, Line Claude 1, Olivier Delattre 1, Michael Paulussen 1, Piero Picci 1, Kirsten Sundby Hall 1, Hendrik van den Berg 1, Ruth Ladenstein 1, Jean Michon 1, Lars Hjorth 1, Ian Judson 1, Roberto Luksch 1, Mark L Bernstein 1, Perrine Marec-Bérard 1, Bernadette Brennan 1, Alan W Craft 1, Richard B Womer 1, Heribert Juergens 1, Odile Oberlin. Ewing sarcoma: current management and future approaches through collaboration. J. Clin. Oncol. 2015. V. 33. № 27. P. 3036–3046.
  34. Rodriguez-Galindo C., Billups C.A., Kun L.E., Rao B.N., Pratt C.B., Merchant T.E., Santana V.M., Pappo A.S. Survival After Recurrence of Ewing Tumors: The St Jude Children's Research Hospital Experience, 1979–1999. Cancer. 2002. V. 94. № 2. P. 561–569.
  35. Bacci G., Ferrari S., Longhi A., Donati D., De Paolis M., Forni C., Versari M., Setola E., Briccoli A., Barbieri E. Therapy and Survival After Recurrence of Ewing's Tumors: The Rizzoli Experience in 195 Patients Treated With Adjuvant and Neoadjuvant Chemotherapy From 1979 to 1997. Ann. Oncol. 2003. V. 14. № 11. P. 1654–1659.
  36. Barker L.M., Pendergrass T.W., Sanders J.E., Hawkins D.S. Survival after recurrence of Ewing's sarcoma family of tumors. J. Clin. Oncol. 2005. V. 23. № 19. P. 4354–4362.
  37. Ohali A., Avigad S., Cohen I.J., Meller I., Kollender Y., Issakov J., Goshen Y., Yaniv I., Zaizov R. High frequency of genomic instability in Ewing family of tumors. Cancer Genet. Cytogenet. 2004. V. 150. № 1. P. 50–66.
  38. Ferreira B.I., Alonso J., Carrillo J., Acquadro F., Largo C., Suela J., Teixeira M.R., Cerveira N., Molares A., Goméz-López G., Pestaña A., Sastre A., Garcia-Miguel P., Cigudosa J.C. Array CGH and gene-expression profiling reveals distinct genomic instability patterns associated with DNA repair and cell-cycle checkpoint pathways in Ewing's sarcoma. Oncogene. 2008. V. 27. № 14. P. 2084–2090.
  39. Machado I., Lopez-Guerrero J.A., Scotlandi K., Picci P., Llombart-Bosch A. Immunohistochemical analysis and prognostic significance of PD-L1, PD1, and CD8+ tumor-infiltrating lymphocytes in Ewing's sarcoma family of tumors (ESFT). Virchows Arch. 2018. V. 472. № 5. P. 815–824.
  40. Kim C., Kim E.K., Jung H., Chon H.J., Han J.W., Shin K.H., Hu H., Kim K.S., Choi Y.D., Kim S., Lee Y.H., Suh J.S., Ahn J.B., Chung H.C., Noh S.H., Rha S.Y., Kim S.H., Kim H.S. Prognostic implications of PD-L1 expression in patients with soft tissue sarcoma. BMC Cancer. 2016. V. 16. P. 434.
  41. Angelini A., Guerra G., Mavrogenis A.F., Pala E., Picci P., Ruggieri P. Clinical outcome of central conventional chondrosarcoma. J. Surg. Oncol. 2012. V. 106. № 8. P. 929–937.
  42. Hogendoorn P.C., Bovée J.V., Nielsen G.P. et al. Chondrosarcoma (grade I-III), including primary and secondary variants and periosteal chondrosarcoma, dedifferentiated chondrosarcoma, mesenchymal chondrosarcoma and clear cell chondrosarcoma. In: Fletcher C.D.M., Bridge J.A., Hogendoorn P.C. et al. (eds.). WHO Classification of Tumours of Soft Tissue and Bone. 4th edn. IARC Press: Lyon, France, 2013. P. 264–274.
  43. Bovée J.V., Hogendoorn P.C., Wunder J.S. et al. Cartilage tumours and bone development: molecular pathology and possible therapeutic targets. Nat. Rev. Cancer. 2010. V. 10. P. 481–488. 
  44. Amary M.F., Bacsi K., Maggiani F. et al. IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J. Pathol. 2011. V. 224. P. 334–343.
  45. Gitelis S., Bertoni F., Picci P., Campanacci M. Chondrosarcoma of bone. The experience at the Istituto Ortopedico Rizzoli. J. Bone Jt. Surg. Am. 1981. V. 63. № 8. P. 1248–1257.
  46. Ahmed A.R., Tan T.S., Unni K.K., Collins M.S., Wenger D.E., Sim F.H. Secondary chondrosarcoma in osteochondroma: report of 107 patients. Clin. Orthop. Relat. Res. 2003. V. 411. P. 193–206.
  47. Guide Line SIOT Study Group. La diagnosi e il trattamento del condrosarcoma. GIOT. 2011. V. 37. P. 18–26.
  48. Gelderblom H., Hogendoorn P.C., Dijkstra S.D., van Rijswijk C.S., Krol A.D., Taminiau A.H., Bovée J.V. The clinical approach towards chondrosarcoma. Oncologist. 2008. V. 13. № 3. P. 320–329.
  49. Riedel R.F., Larrier N., Dodd L., Kirsch D., Martinez S., Brigman B.E. The clinical management of chondrosarcoma. Curr. Treat. Options. Oncol. 2009. V. 10. № 1–2. P. 94–106.
  50. Kostine M., Cleven A.H., de Miranda N.F., Italiano A., Cleton-Jansen A.M., Bovee J.V. Analysis of PD-L1, T-cell infiltrate and HLA expression in chondrosarcoma indicates potential for response to immunotherapy specifically in the dedifferentiated subtype. Mod. Pathol. 2016. V. 29. № 9. P. 1028–1037.
  51. Torabi A., Amaya C.N., Wians F.H. Jr., Bryan B.A. PD-1 and PD-L1 expression in bone and soft tissue sarcomas. Pathology. 2017.  V. 49. № 5. P. 506–513.
  52. Yang X., Zhu G., Yang Z., Zeng K., Liu F., Sun J. Expression of PD-L1/PD-L2 is associated with high proliferation index of Ki-67 but not with TP53 overexpression in chondrosarcoma. Int. J. Biol. Markers. 2018. V. 33. № 4. P. 507–513.
  53. Paoluzzi L., Cacavio A., Ghesani M., Karambelkar A., Rapkiewicz A., Weber J., Rosen G. Response to anti-PD1 therapy with nivolumab in metastatic sarcomas. Clin. Sarcoma Res. 2016. V. 6. P. 24.
  54. Walcott B.P., Nahed B.V., Mohyeldin A., Coumans J.V., Kahle K.T., Ferreira M.J. Chordoma: current concepts, management, and future directions. Lancet Oncol. 2012. V. 13. № 2. P. 69–76.
  55. SEER Cancer Stat Facts: Bone and Joint Cancer. National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/statfacts/html/bones.html
  56. Feng Y., Shen J., Gao Y., Liao Y., Cote G., Choy E., Chebib I., Mankin H., Hornicek F., Duan Z. Expression of programmed cell death ligand 1 (PD-L1) and prevalence of tumor-infiltrating lymphocytes (TILs) in chordoma. Oncotarget. 2015. V. 6. № 13. P. 11139–11149.
  57. Mathios D., Ruzevick J., Jackson C.M., Xu H., Shah S.R., Taube J.M., Burger P.C., McCarthy E.F., Quinones-Hinojosa A., Pardoll D.M., Lim M. PD-1, PD-L1, PD-L2 expression in the chordoma microenvironment. J. Neurooncol. 2015. V. 121. № 2. P. 251–259.
  58. Zou M.X., Peng A.B., Lv G.H., Wang X.B., Li J., She X.L., Jiang Y. Expression of programmed death-1 ligand (PD-L1) in tumorinfiltrating lymphocytes is associated with favorable spinal chordoma prognosis. Am. J. Transl. Res. 2016. V. 8. № 7. P. 3274–3287.
  59. Resnick C.M., Margolis J., Susarla S.M., Schwab J.H., Hornicek F.J., Dodson T.B., Kaban L.B. Maxillofacial and axial/appendicular giant cell lesions: unique tumors or variants of the same disease - A comparison of phenotypic, clinical, and radiographic characteristics. J. Oral. Maxillofac. Surg. 2010. V. 68. P. 130–137.
  60. Balke M., Schremper L., Gebert C., Ahrens H., Streitbuerger A., Koehler G., Hardes J., Gosheger G. Giant cell tumor of bone: treatment and outcome of 214 cases. J. Cancer Res. Clin. Oncol. 2008. V. 134. P. 969–978.
  61. Beebe-Dimmer J.L., Cetin K., Fryzek J.P., Schuetze S.M., Schwartz K. The epidemiology of malignant giant cell tumors of bone: an analysis of data from the Surveillance, Epidemiology and End Results Program (1975–2004). Rare Tumors. 2009. V. 1. e52.
  62. Al-Sukaini A., Hornicek F.J., Peacock Z.S., Kaban L.B., Ferrone S., Schwab J.H. Immune Surveillance Plays a Role in Locally Aggressive Giant Cell Lesions of Bone. Clin. Orthop. Relat. Res. 2017. V. 475. № 12. P. 3071–3081.
  63. Schreuder W.H., Peacock Z.S., Ebb D., Chuang S.K., Kaban L.B. Adjuvant antiangiogenic treatment for aggressive giant cell lesions of the jaw: a 20-year experience at Massachusetts General Hospital. J. Oral Maxillofac. Surg. 2017. V. 75. P. 105–118.
  64. Enneking W.F. A system of staging musculoskeletal neoplasms. Clin. Orthop. Relat. Res. 1986. V. 204. P. 9–24.
  65. Peacock Z.S., Resnick C.M., Susarla S.M., Faquin W.C., Rosenberg A.E., Nielsen G.P., Schwab J.H., Hornicek F., Ebb D.H., Dodson T.B., Kaban L.B. Do histologic criteria predict biologic behavior of giant cell lesions - J. Oral. Maxillofac. Surg. 2012. V. 70. P. 2573–2580.
  66. Branstetter D.G., Nelson S.D., Manivel J.C., Blay J.Y., Chawla S., Thomas D.M., Jun S., Jacobs I. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin. Cancer Res. 2012. V. 18. P. 4415–4424.
  67. Gaston C.L., Grimer R.J., Parry M., Stacchiotti S., Dei Tos A.P., Gelderblom H., Ferrari S., Baldi G.G., Jones R.L., Chawla S., Casali P., LeCesne A., Blay J.Y., Dijkstra S.P., Thomas D.M., Rutkowski P. Current status and unanswered questions on the use of Denosumab in giant cell tumor of bone. Clin. Sarcoma Res. 2016. V. 6. P. 15.
  68. Ghert M., Simunovic N., Cowan R.W., Colterjohn N., Singh G. Properties of the stromal cell in giant cell tumor of bone. Clin. Orthop. Relat. Res. 2007. V. 459. P. 8–13.
  69. Fellenberg J., Saehr H., Lehner B., Depeweg D. A microRNA signature differentiates between giant cell tumor derived neoplastic stromal cells and mesenchymal stem cells. Cancer Lett. 2012. V. 321. P. 162–168.
  70. Sathyanarayanan V., Neelapu S.S. Cancer immunotherapy: strategies for personalization and combinatorial approaches. Mol. Oncol. 2015.  V. 9. P. 2043–2053.
  71. Wang L., Kang F.B., Sun N., Wang J., Chen W., Li D., Shan B.E. The tumor suppressor miR-124 inhibits cell proliferation and invasion by targeting B7-H3 in osteosarcoma. Tumour Biol. 2016. V. 37. № 11. P. 14939–14947.
  72. Frigola X., Inman B.A., Lohse C.M., Krco C.J., Cheville J.C., Thompson R.H., Leibovich B., Blute M.L., Dong H., Kwon E.D. Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma. Clin. Cancer Res. 2011. V. 17. № 7. P. 1915–1923.
  73. Kushlinskij N.E., Alferov A.A., Timofeev YU.S., Gershtejn E.S., Bulycheva I.V., Bondarev A.V., Shchupak M.Yu., Sokolov N.YU., Polikarpova S.B., Efimova M.M., Dzampaev A.A., Sushencov E.A., Aliev M.D., Musaev E.R. Klyuchevye komponenty signal'nogo puti kontrol'noj tochki immuniteta PD-1/PD-L1 v syvorotke krovi pri opuholyah kostej. Byulleten' eksperimental'noj biologii i mediciny. 2020. T. 170. № 7. S. 79–83 (In Russian).
  74. Ding Y., Sun C., Li J., Hu L., Li M., Liu J., Pu L., Xiong S. The Prognostic Significance of Soluble Programmed Death Ligand 1 Expression in Cancers: A Systematic Review and Meta-analysis. Scand. J. Immunol. 2017. V. 86. № 5. P. 361–367.
  75. Zhu X., Lang J. Soluble PD-1 and PD-L1: predictive and prognostic significance in cancer. Oncotarget. 2017. V. 8. № 57. P. 97671–97682.
  76. Wei W., Xu B., Wang Y., Wu C., Jiang J., Wu C. Prognostic significance of circulating soluble programmed death ligand-1 in patients with solid tumors: A meta-analysis. Medicine (Baltimore). 2018. V. 97. № 3. e9617.
Date of receipt: 20.07.2020
Approved after review: 24.08.2020
Accepted for publication: 25.09.2020