PD1/PD1L pathway, HLA-G and T regulatory cells as new markers of immunosuppression in cancers
Paulina Własiuk 1 , Maciej Putowski 1 , Krzysztof Giannopoulos 1Abstract
The appropriate function of the immune system depends on the effective regulation of the immune response on multiple levels. The key element of an effective immune response to antigenic stimulation is maintaining a homeostasis between activation and inhibitory function of immunocompetent cells and molecules. In pathological conditions such as chronic infections, autoimmune diseases or cancer there are significant alterations, and prevalence of signals of one type over another. Main markers of these dysfunctions are altered expressions of molecules, such as programmed death-1 (PD-1), Human Leukocyte Antigen G (HLA-G), or changed percentages of T regulatory cells (Treg). These indicators of immune system dysfunction may contribute to disease progression, but also could represent good targets for treatment. Interestingly, in recent years there are many new, interesting reports which showed that the role of PD-1, HLA-G or Treg is ambiguous and not always their higher expression or frequency lead to the progression of disease. Recent studies have shown that Treg can suppress bacteria-driven inflammation which promotes carcinogenesis and thus protect the host from cancer development. Moreover, proliferation of hematological tumor cells expressing ILT-2 receptor can be inhibited by HLA-G, in contrast to solid tumors where HLA-G favors tumor escape. In this paper we present characteristics of expressions of PD-1 and its ligands, HLA-G, and frequency of Treg cells in a variety of physiological and pathological conditions associated with chronic infections, autoimmune diseases and cancer. The understanding of the complex interactions between the functional elements of immune system is essential for a detailed characteristics of the mechanisms leading to the development of diseases and identification of more effective targeted therapies.
References
- 1. Agata Y., Kawasaki A., Nishimura H., Ishida Y., Tsubata T., YagitaH., Honjo T.: Expression of the PD-1 antigen on the surface of stimulatedmouse T and B lymphocytes. Int. Immunol., 1996; 8: 765-772
Google Scholar - 2. Amiot L., Vu N., Samson M.: Immunomodulatory propertiesof HLA-G in infectious diseases. J. Immunol. Res., 2014; 2014: 1-14
Google Scholar - 3. Amodio G., Comi M., Tomasoni D., Gianolini M.E., Rizzo R., LeMaoultJ., Roncarolo M.G., Gregori S.: HLA-G expression levels influencethe tolerogenic activity of human DC-10. Haematologica,2015; 100: 548-557
Google Scholar - 4. Amodio G., Sales de Albuquerque R., Gregori S.: New insightsinto HLA-G mediated tolerance. Tissue Antig., 2014; 84: 255-263
Google Scholar - 5. Baecher-Allan C., Brown J.A., Freeman G.J., Hafler D.A.:CD4+CD25high regulatory cells in human peripheral blood. J. Immunol.,2001; 167: 1245-1253
Google Scholar - 6. Balkhi M.Y., Ma Q., Ahmad S., Junghans R.P.: T cell exhaustionand Interleukin 2 downregulation. Cytokine, 2015; 71: 339-347
Google Scholar - 7. Barth S.D., Schulze J.J., Kühn T., Raschke E., Hüsing A., JohnsonT., Kaaks R., Olek S.: Treg-mediated immune tolerance and the riskof solid cancers: findings from EPIC-Heidelberg. J. Natl. CancerInst., 2015; 107: djv224
Google Scholar - 8. Bennett C.L., Christie J., Ramsdell F., Brunkow M.E., FergusonP.J., Whitesell L., Kelly T.E., Saulsbury F.T., Chance P.F., Ochs H.D.:The immune dysregulation, polyendocrinopathy, enteropathy, Xlinkedsyndrome (IPEX) is caused by mutations of FOXP3. Nat.Genet., 2001; 27: 20-21
Google Scholar - 9. Bertsias G.K., Nakou M., Choulaki C., Raptopoulou A., PapadPiśmiennictwoimitraki E., Goulielmos G., Kritikos H., Sidiropoulos P., Tzardi M.,Kardassis D., Mamalaki C., Boumpas D.T.: Genetic, immunologic,and immunohistochemical analysis of the programmed death 1/programmed death ligand 1 pathway in human systemic lupuserythematosus. Arthritis Rheum., 2009; 60: 207-218
Google Scholar - 10. Borghaei H., Paz-Ares L., Horn L., Spigel D.R., Steins M., ReadyN.E., Chow L.Q., Vokes E.E., Felip E., Holgado E., Barlesi F., KohlhäuflM., Arrieta O., Burgio M.A., Fayette J. i wsp.: Nivolumab versusdocetaxel in advanced nonsquamous non-small-cell lung cancer.N. Engl. J. Med., 2015; 373: 1627-1639
Google Scholar - 11. Bortolotti D., Gentili V., Rotola A., Cassai E., Rizzo R., Di LucaD.: Impact of HLA-G analysis in prevention, diagnosis and treatmentof pathological conditions. World J. Methodol., 2014; 4: 11-25
Google Scholar - 12. Carosella E.D., Gregori S., LeMaoult J.: The tolerogenicinterplay(s) among HLA-G, myeloid APCs, and regulatory cells.Blood, 2011; 118: 6499-6505
Google Scholar - 13. Carosella E.D., Moreau P., Le Maoult J., Le Discorde M., DaussetJ., Rouas-Freiss N.: HLA-G molecules: from maternal-fetal toleranceto tissue acceptance. Adv. Immunol., 2003; 81: 199-252
Google Scholar - 14. Carosella E.D., Moreau P., LeMaoult J., Rouas-Freiss N.: HLAG:from biology to clinical benefits. Trends Immunol., 2008; 29:125-132
Google Scholar - 15. Carosella E.D., Rouas-Freiss N., Roux D.T., Moreau P., Le MaoultJ.: HLA-G: an immune checkpoint molecule. Adv. Immunol., 2015;157: 33-144
Google Scholar - 16. Caumartin J., Favier B., Daouya M., Guillard C., Moreau P., Carosella E.D., Le Maoult J.: Trogocytosis-based generation of suppressiveNK cells. EMBO J., 2007; 26: 1423-1433
Google Scholar - 17. Chen J., Shen B., Jiang Y., Jun L., Zhu M., Chen B., Liu C.: Analysisof immunoglobulin-like transcripts (ILTs) in lymphocytes with sHLA-Gand IL10 from SLE patients. Clin. Exp. Med., 2013; 13: 135-142
Google Scholar - 18. Contini P., Ghio M., Poggi A., Filaci G., Indiveri F., Ferrone S.,Puppo F.: Soluble HLA-A,-B,-C and -G molecules induce apoptosisin T and NK CD8+ cells and inhibit cytotoxic T cell activity throughCD8 ligation. Eur. J. Immunol., 2003; 33: 125-134
Google Scholar - 19. Cooper G.S., Bynum M.L., Somers E.C.: Recent insights in theepidemiology of autoimmune diseases: improved prevalence estimatesand understanding of clustering of diseases. J. Autoimmun.,2009; 33: 197-207
Google Scholar - 20. Cosmi L., Liotta F., Lazzeri E., Francalanci M., Angeli R., MazzinghiB., Santarlasci V., Manetti R., Vanini V., Romagnani P., MaggiE., Romagnani S., Annunziato F.: Human CD8 + CD25 + thymocytesshare phenotypic and functional features with CD4 + CD25 + regulatorythymocytes. Blood, 2003; 102: 4107-4114
Google Scholar - 21. Cottrez F., Groux H.: Specialization in tolerance: innate CD(4+)CD(25+) versus acquired TR1 and TH3 regulatory T cells. Transplantation,2004; 77: 12-15
Google Scholar - 22. Crusz S.M., Balkwill F.R.: Inflammation and cancer: advancesand new agents. Nat. Rev. Clin. Oncol., 2015; 12: 584-596
Google Scholar - 23. Danke N.A., Koelle D.M., Yee C., Beheray S., Kwok W.W.: AutoreactiveT cells in healthy individuals. J. Immunol., 2004; 172:5967-5972
Google Scholar - 24. Dong H., Strome S.E., Salomao D.R., Tamura H., Hirano F., FliesD.B., Roche P.C., Lu J., Zhu G., Tamada K., Lennon V.A., Celis E., ChenL.: Tumor-associated B7-H1 promotes T-cell apoptosis: A potentialmechanism of immune evasion. Nat. Med., 2002; 8: 793-800
Google Scholar - 25. Dorfman D.M., Brown J.A., Shahsafaei A., Freeman G.J: ProgrammedDeath-1 (PD-1) is a marker of germinal center-associatedT cells and angioimmunoblastic T-cell lymphoma. Am. J. Surg.Pathol., 2006; 30: 802-810
Google Scholar - 26. Elkord E.: Role of regulatory T cells in allergy: implicationsfor therapeutic strategy. Inflamm. Allergy Drug Targets, 2006; 5:211-217
Google Scholar - 27. Facciabene A., Motz G.T., Coukos G.: T-regulatory cells: keyplayers in tumor immune escape and angiogenesis. Cancer Res.,2012; 72: 2162-2171
Google Scholar - 28. Fehérvari Z., Sakaguchi S.: CD4+ Tregs and immune control. J.Clin. Invest. 2004; 114: 1209-1217
Google Scholar - 29. 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. i wsp.: Engagementof the PD-1 immunoinhibitory receptor by a novel B7family member leads to negative regulation of lymphocyte activation.J. Exp. Med., 2000; 192: 1027-1034
Google Scholar - 30. Freeman G.J., Wherry E.J., Ahmed R., Sharpe A.H.: Reinvigoratingexhausted HIV-specific T cells via PD-1-PD-1 ligand blockade.J. Exp. Med., 2006; 203: 2223-2227
Google Scholar - 31. Gallimore A., Glithero A., Godkin A., Tissot A.C., Plückthun A.,Elliott T., Hengartner H., Zinkernagel R.: Induction and exhaustionof lymphocytic choriomeningitis virus-specific cytotoxic Tlymphocytes visualized using soluble tetrameric major histocompatibilitycomplex class I-peptide complexes. J. Exp. Med., 1998;187: 1383-1393
Google Scholar - 32. Gao Q., Qiu S.J., Fan J., Zhou J., Wang X.Y., Xiao Y.S., Xu Y., LiY.W., Tang Z.Y.: Intratumoral balance of regulatory and cytotoxicT cells is associated with prognosis of hepatocellular carcinomaafter resection. J. Clin. Oncol., 2007; 25: 2586-2593
Google Scholar - 33. Geis A.L., Fan H., Wu X., Wu S., Huso D.L., Wolfe J.L., Sears C.L.,Pardoll D.M., Housseau F.: Regulatory T cell response to enterotoxigenicBacteroides fragilis colonization triggers IL-17-dependentcolon carcinogenesis. Cancer Discov., 2015; 5: 1098-1109
Google Scholar - 34. Ghebeh H., Mohammed S., Al-Omair A., Qattan A., Lehe C., AlQudaihiG., Elkum N., Alshabanah M., Bin Amer S., Tulbah A., AjarimD., Al-Tweigeri T., Dermime S.: The B7-H1 (PD-L1) T lymphocyteinhibitorymolecule is expressed in breast cancer patients withinfiltrating ductal carcinoma: correlation with important high-riskprognostic factors. Neoplasia, 2006; 8: 190-198
Google Scholar - 35. Gianchecchi E., Delfino D.V., Fierabracci A.: Recent insightsinto the role of the PD-1/PD-L1 pathway in immunological toleranceand autoimmunity. Autoimmun. Rev., 2013; 12: 1091-1100
Google Scholar - 36. Giannopoulos K., Dmoszyńska A., Bojarska-Junak A., SchmittM., Roliński J.: Expression of HLA-G in patients with B-cell chroniclymphocytic leukemia (B-CLL). Folia Histochem. Cytobiol., 2008;46: 457-460
Google Scholar - 37. Giannopoulos K., Kaminska W., Hus I., Dmoszyńska A.: Thefrequency of T regulatory cells modulates the survival of multiplemyeloma patients: detailed characterisation of immune status inmultiple myeloma. Br. J. Cancer, 2012; 106: 546-552
Google Scholar - 38. Giannopoulos K., Schmitt M., Kowal M., Wlasiuk P., BojarskaJunakA., Chen J., Rolinski J., Dmoszynska A.: Characterization ofregulatory T cells in patients with B-cell chronic lymphocytic leukemia.Oncol. Rep., 2008; 20: 677-682
Google Scholar - 39. Giannopoulos K., Schmitt M,. Kowal M., Własiuk P., BojarskaJunakA., Roliński J., Dmoszyńska A.: The significance of solubleHLA-G plasma levels as well as messenger HLA-G for B-cell chroniclymphocytic leukemia (B-CLL). Leuk. Res., 2008; 32: 1815-1819
Google Scholar - 40. Gizinski A.M., Fox D.A.: T cell subsets and their role in thepathogenesis of rheumatic disease. Curr. Opin. Rheumatol., 2014;26: 204-210
Google Scholar - 41. Good-Jacobson K.L., Szumilas C.G., Chen L., Sharpe A.H., TomaykoM.M., Shlomchik M.J.: PD-1 regulates germinal center B cellsurvival and the formation and affinity of long-lived plasma cells.Nat. Immunol., 2010; 11: 535-542
Google Scholar - 42. Gregg R., Smith C.M., Clark F.J., Dunnion D., Khan N., ChakravertyR., Nayak L, Moss P.A.: The number of human peripheralblood CD4+ CD25high regulatory T cells increases with age. Clin.Exp. Immunol., 2005; 140: 540-546
Google Scholar - 43. Grzywnowicz M, Karabon L, Karczmarczyk A, Zajac M, SkorkaK, Zaleska J, Wlasiuk P., Chocholska S., Tomczak W., Bojarska-JunakA., Dmoszynska A., Frydecka I., Giannopoulos K.: The function ofa novel immunophenotype candidate molecule PD-1 in chroniclymphocytic leukemia. Leuk. Lymph., 2015; 56: 2908-2913
Google Scholar - 44. Grzywnowicz M., Zaleska J., Mertens D., Tomczak W., WlasiukP., Kosior K., Piechnik A., Bojarska-Junak A., Dmoszynska A., GiannopoulosK.: Programmed death-1 and its ligand are novel immunotolerantmolecules expressed on leukemic B cells in chroniclymphocytic leukemia. PLoS One, 2012; 7: e35178
Google Scholar - 45. Guo Q.Y., Chen B.G., Ruan Y.Y., Lin A., Yan W.H.: HLA-G expressionis irrelevant to prognosis in patients with acute myeloid leukemia.Leuk. Res., 2011; 35: 1350-1354
Google Scholar - 46. Guo Z.Y., Lv Y.G., Wang L., Shi S.J., Yang F., Zheng G.X., WenW.H., Yang A.G.: Predictive value of HLA-G and HLA-E in the prognosisof colorectal cancer patients. Cell Immunol., 2015; 293: 10-16
Google Scholar - 47. Hamanishi J., Mandai M., Iwasaki M., Okazaki T., Tanaka Y., YamaguchiK., Higuchi T., Yagi H., Takakura K., Minato N., Honjo T.,Fujii S.: Programmed cell death 1 ligand 1 and tumor-infiltratingCD8+ T lymphocytes are prognostic factors of human ovarian cancer.Proc. Natl. Acad. Sci. USA, 2007; 104: 3360-3365
Google Scholar - 48. Hamanishi J., Mandai M., Matsumura N., Abiko K., Baba T.,Konishi I.: PD ‑ 1/PD ‑ L1 blockade in cancer treatment: perspectivesand issues. Int. J. Clin. Oncol., 2016; 21: 462-473
Google Scholar - 49. He X., Dong D.D., Yie S.M., Yang H., Cao M., Ye S.R., Li K., LiuJ., Chen J.: HLA-G expression in human breast cancer: implicationsfor diagnosis and prognosis, and effect on allocytotoxic lymphocyteresponse after hormone treatment in vitro. Ann. Surg. Oncol.,2010; 17: 1459-1469
Google Scholar - 50. Hviid T.V., Rizzo R., Melchiorri L., Stignani M., Baricordi O.R.:Polymorphism in the 5′ upstream regulatory and 3′ untranslatedregions of the HLA-G gene in relation to soluble HLA-G and IL-10expression. Hum. Immunol., 2006; 67: 53-62
Google Scholar - 51. Ishida Y., Agata Y., Shibahara K., Honjo T.: Induced expressionof PD-1, a novel member of the immunoglobulin gene superfamily,upon programmed cell death. EMBO J. 1992; 11: 3887-3895
Google Scholar - 52. Jiao Q., Liu C., Yang Z., Ding Q., Wang M., Li M., Zhu T., QianH., Li W., Tu N., Fang F., Ye L., Zhao Z., Qian Q.: Upregulated PD-1expression is associated with the development of systemic lupuserythematosus, but not the PD-1.1 Allele of the PDCD1 gene. Int.J. Genomics. 2014; 2014: 950903
Google Scholar - 53. Josefowicz S.Z., Lu L.F., Rudensky A.Y.: Regulatory T cells: mechanismsof differentiation and function. Annu. Rev. Immunol.,2012; 30: 531-564
Google Scholar - 54. Jung Y.W., Kim Y.T., Kim S.W., Kim S., Kim J.H., Cho N.H., KimJ.W.: Correlation of human leukocyte antigen-G (HLA-G) expressionand disease progression in epithelial ovarian cancer. Reprod.Sci., 2009; 16: 1103-1111
Google Scholar - 55. Kasagi S., Kawano S., Kumagai S.: PD-1 and autoimmunity. Crit.Rev. Immunol., 2011; 31: 265-295
Google Scholar - 56. Keir M.E., Butte M.J., Freeman G.J., Sharpe A.H.: PD-1 and itsligands in tolerance and immunity. Annu. Rev. Immunol., 2008;26: 677-704
Google Scholar - 57. Keir M.E., Liang S.C., Guleria I., Latchman Y.E., Qipo A., AlbackerL.A., Koulmanda M., Freeman G.J., Sayegh M.H., Sharpe A.H.:Tissue expression of PD-L1 mediates peripheral T cell tolerance.J. Exp. Med., 2006; 203: 883-895
Google Scholar - 58. Kinter A.L., Godbout E.J., McNally J.P., Sereti I., Roby G.A.,O’Shea M.A., Fauci A.S.: The common g-chain cytokines IL-2, IL-7,IL-15, and IL-21 induce the expression of programmed death-1 andits ligands. J. Immunol., 2008; 181: 6738-6746
Google Scholar - 59. Kiyasu J., Miyoshi H., Hirata A., Arakawa F., Ichikawa A., NiinoD., Sugita Y., Yufu Y., Choi I., Abe Y., Uike N., Nagafuji K., OkamuraT., Akashi K., Takayanagi R. i wsp.: Expression of programmed celldeath ligand 1 is associated with poor overall survival in patientswith diffuse large B-cell lymphoma. Blood, 2015; 126: 2193-2201
Google Scholar - 60. Konishi J., Yamazaki K., Azuma M., Kinoshita I., Dosaka-AkitaH., Nishimura M.: B7-H1 expression on non-small cell lung cancercells and its relationship with tumor-infiltrating lymphocytesand their PD-1 expression. Clin. Cancer Res., 2004; 10: 5094-5100
Google Scholar - 61. Kristjansdottir H., Steinsson K., Gunnarsson I., Gröndal G.,Erlendsson K., Alarcón-Riquelme M.E.: Lower expression levels ofthe programmed death 1 receptor on CD4+CD25+ T cells and correlationwith the PD-1.3A genotype in patients with systemic lupuserythematosus. Arthritis. Rheum., 2010; 62: 1702-1711
Google Scholar - 62. Ladoire S., Arnould L., Mignot G., Coudert B., Rébé C., ChalminF., Vincent J., Bruchard M., Chauffert B., Martin F., FumoleauP., Ghiringhelli F.: Presence of Foxp3 expression in tumor cellspredicts better survival in HER2-overexpressing breast cancer patientstreated with neoadjuvant chemotherapy. Breast Cancer Res.Treat., 2011; 125: 65-72
Google Scholar - 63. Le Bouteiller P., Mallet V.: HLA-G and pregnancy. Rev. Reprod.,1997; 2: 7-13
Google Scholar - 64. Leleu X., Le Friec G., Facon T., Amiot L., Fauchet R., HennacheB., Coiteux V., Yakoub-Agha I., Dubucquoi S., Avet-Loiseau H., MathiotC., Bataille R., Mary J.Y.: Total soluble HLA class I and solubleHLA-G in multiple myeloma and monoclonal gammopathy of undetermined significance. Clin. Cancer Res., 2005; 11: 7297-7303
Google Scholar - 65. Le Maoult J., Le Discorde M., Rouas-Freiss N., Moreau P., MenierC., McCluskey J., Carosella E.D.: Biology and functions of humanleukocyte antigen-G in health and sickness. Tiss. Antig. 2003;62: 273-284
Google Scholar - 66. Li B.L., Lin A., Zhang X.J., Zhang X., Zhang J.G., Wang Q., ZhouW.J., Chen H.X., Wang T.J., Yan W.H.: Characterization of HLA-Gexpression in renal cell carcinoma. Tiss. Antig. 2009; 74: 213-221
Google Scholar - 67. Li S., Liao W., Chen M., Shan S., Song Y., Zhang S., Song H., YuanZ.: Expression of programmed death-1 (PD-1) on CD4+ and CD8+T cells in rheumatoid arthritis. Inflammation, 2014; 37: 116-121
Google Scholar - 68. Liang S.C., Latchman Y.E., Buhlmann J.E., Tomczak M.F., HorwitzB.H., Freeman G.J., Sharpe A.H.: Regulation of PD-1, PD-L1,and PD-L2 expression during normal and autoimmune responses.Eur. J. Immunol., 2003; 33: 2706-2716
Google Scholar - 69. Lim H.W., Hillsamer P., Banham A.H., Kim C.H.: Cutting edge:direct suppression of B cells by CD4+ CD25+ regulatory T cells. J.Immunol., 2005; 175: 4180-4183
Google Scholar - 70. Lin A., Chen H.X., Zhu C.C., Zhang X., Xu H.H., Zhang J.G.,Wang Q., Zhou W.J., Yan W.H.: Aberrant human leucocyte antigen-Gexpression and its clinical relevance in hepatocellular carcinoma.J. Cell Mol. Med., 2010; 14: 2162-2171
Google Scholar - 71. Lin A., Zhu C.C., Chen H.X., Chen B.F., Zhang X., Zhang J.G.,Wang Q., Zhou W.J., Hu W., Yang H.H., Xu H.H., Yan W.H.: Clinicalrelevance and functional implications for human leucocyte antigen-gexpression in non-small-cell lung cancer. J. Cell Mol. Med.,2010; 14: 2318-2329
Google Scholar - 72. Lin H., Mosmann T.R., Guilbert L,. Tuntipopipat S., WegmannT.G.: Synthesis of T helper 2-type cytokines at the maternal-fetalinterface. J. Immunol., 1993; 151: 4562-4573
Google Scholar - 73. Liu J., Hamrouni A., Wolowiec D., Coiteux V., Kuliczkowski K.,Hetuin D., Saudemont A., Quesnel B.: Plasma cells from multiplemyeloma patients express B7-H1 (PD-L1) and increase expressionafter stimulation with IFN-g and TLR ligands via a MyD88-, TRAF6-,and MEK-dependent pathway. Blood, 2007; 110: 296-304
Google Scholar - 74. Locafaro G., Amodio G., Tomasoni D., Tresoldi C., Ciceri F.,Gregori S.: HLA-G expression on blasts and tolerogenic cells inpatients affected by acute myeloid leukemia. J. Immunol. Res.,2014; 2014: 636292
Google Scholar - 75. Miracco C., Mourmouras V., Biagioli M., Rubegni P., MannucciS., Monciatti I., Cosci E., Tosi P., Luzi P.: Utility of tumour-infiltratingCD25+FOXP3+ regulatory T cell evaluation in predicting localrecurrence in vertical growth phase cutaneous melanoma. Oncol.Rep., 2007; 18: 1115-1122
Google Scholar - 76. Myklebust J.H., Irish J.M., Brody J., Czerwinski D.K., Houot R.,Kohrt H.E., Timmerman J., Said J., Green M.R., Delabie J., KolstadA., Alizadeh A.A., Levy R.: High PD-1 expression and suppressedcytokine signaling distinguish T cells infiltrating follicular lymphomatumors from peripheral T cells. Blood, 2013; 121: 1367-1376
Google Scholar - 77. Nagaraj S., Youn J.I., Gabrilovich D.I.: Reciprocal relationshipbetween myeloid-derived suppressor cells and T cells. J. Immunol.,2013; 191: 17-23
Google Scholar - 78. Naji A., Menier C., Maki G., Carosella E.D., Rouas-Freiss N.:Neoplastic B-cell growth is impaired by HLA-G/ILT2 interaction.Leukemia, 2012; 26: 1889-1892
Google Scholar - 79. Nie J., Li Y.Y., Zheng S.G., Tsun A., Li B.: FOXP3(+) Treg cells andgender bias in autoimmune diseases. Front. Immunol., 2015; 6: 493
Google Scholar - 80. Nishimura H., Agata Y., Kawasaki A., Sato M., Imamura S., MinatoN., Yagita H., Nakano T., Honjo T.: Developmentally regulatedexpression of the PD-1 protein on the surface of double-negative(CD4-CD8-) thymocytes. Int. Immunol., 1996; 8: 773-780
Google Scholar - 81. Nishimura H., Honjo T., Minato N.: Facilitation of β selection and modification of positive selection in the thymus of PD-1-deficientmice. J. Exp. Med., 2000; 191: 891-898
Google Scholar - 82. O’Connor R.A., Anderton S.M.: Inflammation-associated genes:risks and benefits to Foxp3+ Treg function. Immunology, 2015:146: 194-205
Google Scholar - 83. Oestreich K.J., Yoon H., Ahmed R., Boss J.M.: NFATc1 regulatesPD-1 expression upon T cell activation. J. Immunol., 2008;181: 4832-4839
Google Scholar - 84. Ohigashi Y., Sho M., Yamada Y., Tsurui Y., Hamada K., IkedaN., Mizuno T., Yoriki R., Kashizuka H., Yane K., Tsushima F., OtsukiN., Yagita H., Azuma M., Nakajima Y.: Clinical significance ofProgrammed Death-1Ligand-1 and Programmed Death-1Ligand-2expression in human esophageal cancer. Clin. Cancer Res., 2005;11: 2947-2953
Google Scholar - 85. Ohl K., Tenbrock K.: Regulatory T cells in systemic lupus erythematosus.Eur. J. Immunol., 2015; 45: 344-355
Google Scholar - 86. Okazaki T., Honjo T.: PD-1 and PD-1 ligands: from discovery toclinical application. Int. Immunol., 2007; 19: 813-824
Google Scholar - 87. Ostapchuk E.O., Perfi L’eva Y.V., Talaeva S.Z., Omarbaeva N.A.,Belyaev N.N.: Content of HLA-G+ T cells in the peripheral bloodfrom healthy women and breast cancer patients. Bull. Exp. Biol.Med., 2015; 159: 649-651
Google Scholar - 88. Pan Y.Q., Ruan Y.Y., Peng J.B., Han Q.Y., Zhang X., Lin A., YanW.H.: Diagnostic significance of soluble human leukocyte antigen-Gfor gastric cancer. Hum. Immunol., 2016; 77: 317-324
Google Scholar - 89. Pauken K.E., Wherry E.J.: Overcoming T cell exhaustion in infectionand cancer. Trends Immunol., 2015; 36: 265-276
Google Scholar - 90. Paul P., Cabestre F.A., Ibrahim E.C., Lefebvre S., Khalil-Daher I.,Vazeux G., Quiles R.M., Bermond F., Dausset J., Carosella E.D.: Identificationof HLA-G7 as a new splice variant of the HLA-G mRNA andexpression of soluble HLA-G5, -G6, and -G7 transcripts in humantransfected cells. Hum. Immunol., 2000; 61: 1138-1149
Google Scholar - 91. Prokunina L., Castillejo-López C., Oberg F., Gunnarsson I.,Berg L., Magnusson V., Brookes A.J., Tentler D., Kristjansdóttir H.,Gröndal G., Bolstad A.I., Svenungsson E., Lundberg I., Sturfelt G.,Jönssen A. i wsp.: A regulatory polymorphism in PDCD1 is associatedwith susceptibility to systemic lupus erythematosus in humans.Nat. Genet., 2002; 32: 666-669
Google Scholar - 92. Prokunina L., Gunnarsson I., Sturfelt G., Truedsson L., SeligmanV.A., Olson J.L., Seldin M.F., Criswell L.A., Alarcón-RiquelmeM.E.: The systemic lupus erythematosus-associated PDCD1 polymorphismPD1.3A in lupus nephritis. Arthritis Rheum., 2004; 50:327-328
Google Scholar - 93. Riley J.L.: PD-1 signaling in primary T cells. Immunol. Rev.,2009; 229: 114-125
Google Scholar - 94. Rizzo R., Bortolotti D., Bolzani S., Fainardi E.: HLA-G moleculesin autoimmune diseases and infections. Front Immunol.,2014; 5: 592
Google Scholar - 95. Rizzo R., Hviid T.V., Govoni M., Padovan M., Rubini M., MelchiorriL., Stignani M., Carturan S., Grappa M.T., Fotinidi M., FerrettiS., Voss A., Laustrup H., Junker P., Trotta F. i wsp.: HLA-G genotypeand HLA-G expression in systemic lupus erythematosus: HLA-G asa putative susceptibility gene in systemic lupus erythematosus.Tiss. Antig., 2008; 71: 520-529
Google Scholar - 96. Robert C., Long G.V., Brady B., Dutriaux C., Maio M., MortierL., Hassel J.C., Rutkowski P., McNeil C., Kalinka-Warzocha E., SavageK.J., Hernberg M.M., Lebbé C., Charles J., Mihalcioiu C. i wsp.:Nivolumab in previously untreated melanoma without BRAF mutation.N. Engl. J. Med., 2015; 372: 320-330
Google Scholar - 97. Rouas-Freiss N., Goncalves R.M., Menier C., Dausset J., CarosellaE.D.: Direct evidence to support the role of HLA-G in protectingthe fetus from maternal uterine natural killer cytolysis. Proc. Natl.Acad. Sci. USA, 1997; 94: 11520-11525
Google Scholar - 98. Rouas-Freiss N., Moreau P., LeMaoult J., Carosella E.D.: Thedual role of HLA-G in cancer. J. Immunol. Res., 2014; 2014: 359748
Google Scholar - 99. Sakaguchi S., Sakaguchi N., Asano M., Itoh M., Toda M.: Immunologicself-tolerance maintained by activated T cells expressingIL-2 receptor alpha-chains (CD25). Breakdown of a single mechanismof self-tolerance causes various autoimmune diseases. J. Immunol.,1995; 155: 1151-1164
Google Scholar - 100. Schiering C., Krausgruber T., Chomka A., Fröhlich A., AdelmannK., Wohlfert E.A., Pott J., Griseri T., Bollrath J., Hegazy A.N.,Harrison O.J., Owens B.M., Löhning M., Belkaid Y., Fallon P.G. i wsp.:The alarmin IL-33 promotes regulatory T-cell function in the intestine.Nature, 2014; 513: 564-568
Google Scholar - 101. Shimauchi T., Kabashima K., Nakashima D., Sugita K., YamadaY., Hino R., Tokura Y.: Augmented expression of programmeddeath-1 in both neoplastic and non-neoplastic CD4+ T-cells in adultT-cell leukemia/lymphoma. Int. J. Cancer, 2007; 121: 2585-2590
Google Scholar - 102. Speiser D.E., Utzschneider D.T., Oberle S.G., Münz C., RomeroP., Zehn D.: T cell differentiation in chronic infection and cancer:functional adaptation or exhaustion? Nat. Rev. Immunol., 2014;14: 768-774
Google Scholar - 103. Tao H., Mimura Y., Aoe K., Kobayashi S., Yamamoto H., MatsudaE., Okabe K., Matsumoto T., Sugi K., Ueoka H.: Prognosticpotential of FOXP3 expression in non-small cell lung cancer cellscombined with tumor-infiltrating regulatory T cells. Lung Cancer,2012; 75: 95-101
Google Scholar - 104. Thompson R.H., Gillett M.D., Cheville J.C., Lohse C.M., DongH., Webster W.S., Krejci K.G., Lobo J.R., Sengupta S., Chen L., ZinckeH., Blute M.L., Strome S.E., Leibovich B.C., Kwon E.D.: CostimulatoryB7-H1 in renal cell carcinoma patients: Indicator of tumoraggressiveness and potential therapeutic target. Proc. Natl. Acad.Sci. USA, 2004; 101: 17174-17179
Google Scholar - 105. Tzankov A., Meier C., Hirschmann P., Went P., Pileri S.A.,Dirnhofer S.: Correlation of high numbers of intratumoral FOXP3+regulatory T cells with improved survival in germinal center-likediffuse large B-cell lymphoma, follicular lymphoma and classicalHodgkin’s lymphoma. Haematologica, 2008; 93: 193-200
Google Scholar - 106. Vigano S., Perreau M., Pantaleo G., Harari A.: Positive andnegative regulation of cellular immune responses in physiologicconditions and diseases. Clin. Dev. Immunol., 2012; 2012: 485781
Google Scholar - 107. Wastowski I.J., Simões R.T., Yaghi L., Donadi E.A., Pancoto J.T.,Poras I., Lechapt-Zalcman E., Bernaudin M., Valable S., Carlotti C.G.Jr, Flajollet S., Jensen S.S., Ferrone S., Carosella E.D., KristensenB.W. i wsp.: Human leukocyte antigen-G is frequently expressed inglioblastoma and may be induced in vitro by combined 5-aza-2’-deoxycytidine and interferon-γ treatments: results from a multicentricstudy. Am. J. Pathol., 2013; 182: 540-552
Google Scholar - 108. Weinstock M., McDermott D.: Targeting PD-1/PD-L1 in thetreatment of metastatic renal cell carcinoma. Ther. Adv. Urol.,2015; 7: 365-377
Google Scholar - 109. Wherry E.J., Kurachi M.: Molecular and cellular insights intoT cell exhaustion. Nat. Rev. Immunol., 2015; 15: 486-499
Google Scholar - 110. Własiuk P., Niedzielski A., Skorka K., Karczmarczyk A., ZaleskaJ., Zajac M., Putowski M., Pac-Kozuchowska E., Giannopoulos K.: Accumulationof CD5+CD19+ B lymphocytes expressing PD-1 and PD-1Lin hypertrophied pharyngeal tonsils. Clin. Exp. Med., 2015 (w druku)
Google Scholar - 111. Własiuk P., Stec A., Piechnik A., Kaminska W., DmoszynskaA., Ksiazek A., Giannopoulos K.: Expression of soluble HLA-G inmultiple myeloma patients and patients with renal failure. Leuk.Res., 2012; 36: 881-883
Google Scholar - 112. Własiuk P., Steć A., Świder R., Durlik M., Giannopoulos K.,Książek A.: Association between increased levels of regulatory Tcells and soluble human leukocyte antigen G with the prevalenceof cancer in kidney transplant recipients. Pol. Arch. Med. Wewn.,2015; 125: 779-782
Google Scholar - 113. Własiuk P., Tomczak W., Zając M., Dmoszyńska A., GiannopoulosK.: Total expression of HLA-G and TLR-9 in chronic lymphocyticleukemia patients. Hum. Immunol., 2013; 74: 1592-1597
Google Scholar - 114. Xerri L., Chetaille B., Serriari N., Seriari N., Attias C., GuillaumeY., Arnoulet C., Olive D.: Programmed death 1 is a markerof angioimmunoblastic T-cell lymphoma and B-cell small lymphocyticlymphoma/chronic lymphocytic leukemia. Hum. Pathol.,2008; 39: 1050-1058
Google Scholar - 115. Yamazaki T., Akiba H., Iwai H., Matsuda H., Aoki M., Tanno Y.,Shin T., Tsuchiya H., Pardoll D.M., Okumura K., Azuma M., YagitaH.: Expression of Programmed Death 1 ligands by murine T cellsand APC. J. Immunol., 2002; 169: 5538-5545
Google Scholar - 116. Yan M., Jene N., Byrne D., Millar E.K., O’Toole S.A., McNeilC.M., Bates G.J., Harris A.L., Banham A.H., Sutherland R.L., FoxS.B.: Recruitment of regulatory T cells is correlated with hypoxiainducedCXCR4 expression, and is associated with poor prognosis in basal-like breast cancers. Breast Canc. Res., 2011; 13: R47
Google Scholar - 117. Yang Z.Z., Novak A.J., Stenson M.J., Witzig T.E., Ansell S.M.:Intratumoral CD4+CD25+ regulatory T-cell-mediated suppressionof infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma. Blood,2006; 107: 3639-3646
Google Scholar - 118. Zajac A.J., Blattman J.N., Murali-Krishna K., Sourdive D.J.,Suresh M., Altman J.D., Ahmed R.: Viral immune evasion due topersistence of activated T cells without effector function. J. Exp.Med., 1998; 188: 2205-2213
Google Scholar - 119. 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., AlmoS.C.: Structural and functional analysis of the costimulatory receptorprogrammed death-1. Immunity, 2004; 20: 337-347
Google Scholar