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  • Pages.30.1-30.16
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  • 2024
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  • 1598-2629(pISSN)
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  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
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Multi-Layered Mechanisms of Immunological Tolerance at the Maternal-Fetal Interface

  • Jin Soo Joo (Department of Systems Biology, Yonsei University) ;
  • Dongeun Lee (Department of Systems Biology, Yonsei University) ;
  • Jun Young Hong (Department of Systems Biology, Yonsei University)
  • 투고 : 2024.04.12
  • 심사 : 2024.07.08
  • 발행 : 2024.08.31
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초록

Pregnancy represents an immunological paradox where the maternal immune system must tolerate the semi-allogeneic fetus expressing paternally-derived Ags. Accumulating evidence over decades has revealed that successful pregnancy requires the active development of robust immune tolerance mechanisms. This review outlines the multi-layered processes that establish fetomaternal tolerance, including the physical barrier of the placenta, restricted chemokine-mediated leukocyte trafficking, lack of sufficient alloantigen presentation, the presence of immunosuppressive regulatory T cells and tolerogenic decidual natural killer cells, expression of immune checkpoint molecules, specific glycosylation patterns conferring immune evasion, and unique metabolic/hormonal modulations. Interestingly, many of the strategies that enable fetal tolerance parallel those employed by cancer cells to promote angiogenesis, invasion, and immune escape. As such, further elucidating the mechanistic underpinnings of fetal-maternal tolerance may reciprocally provide insights into developing novel cancer immunotherapies as well as understanding the pathogenesis of gestational complications linked to dysregulated tolerance processes.

키워드

과제정보

We apologize that we cannot cite all the seminal papers on this subject. This work was supported by the Yonsei Research Fund (2023-22-0102), Young Medical Scientist Research Grant through the Daewoong Foundation (DFY2301P), and the National Research Foundation of Korea, Ministry of Science, Information and Communication Technology (ICT) and Future Planning NRF-2022R1C1C1007283.

참고문헌

  1. Moffett A, Loke YW. The immunological paradox of pregnancy: a reappraisal. Placenta 2004;25:1-8.
  2. Billingham RE, Brent L, Medawar PB. Actively acquired tolerance of foreign cells. Nature 1953;172:603-606.
  3. Woodruff MF. Transplantation immunity and the immunological problem of pregnancy. Proc R Soc Lond B Biol Sci 1958;148:68-75.
  4. Beer AE, Billingham RE. Implantation, transplantation, and epithelial-mesenchymal relationships in the rat uterus. J Exp Med 1970;132:721-736.
  5. Bowman JM. The prevention of Rh immunization. Transfus Med Rev 1988;2:129-150.
  6. Girardi G, Yarilin D, Thurman JM, Holers VM, Salmon JE. Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J Exp Med 2006;203:2165-2175.
  7. McKelvey KJ, Yenson VM, Ashton AW, Morris JM, McCracken SA. Embryonic/fetal mortality and intrauterine growth restriction is not exclusive to the CBA/J sub-strain in the CBA×DBA model. Sci Rep 2016;6:35138.
  8. Petitbarat M, Durigutto P, Macor P, Bulla R, Palmioli A, Bernardi A, De Simoni MG, Ledee N, Chaouat G, Tedesco F. Critical role and therapeutic control of the lectin pathway of complement activation in an abortion-prone mouse mating. J Immunol 2015;195:5602-5607.
  9. Jin LP, Zhou YH, Wang MY, Zhu XY, Li DJ. Blockade of CD80 and CD86 at the time of implantation inhibits maternal rejection to the allogeneic fetus in abortion-prone matings. J Reprod Immunol 2005;65:133-146.
  10. Erlebacher A, Vencato D, Price KA, Zhang D, Glimcher LH. Constraints in antigen presentation severely restrict T cell recognition of the allogeneic fetus. J Clin Invest 2007;117:1399-1411.
  11. Tay CS, Tagliani E, Collins MK, Erlebacher A. Cis-acting pathways selectively enforce the non-immunogenicity of shed placental antigen for maternal CD8 T cells. PLoS One 2013;8:e84064.
  12. Perchellet AL, Jasti S, Petroff MG. Maternal CD4+ and CD8+ T cell tolerance towards a fetal minor histocompatibility antigen in T cell receptor transgenic mice. Biol Reprod 2013;89:102.
  13. Kahn DA, Baltimore D. Pregnancy induces a fetal antigen-specific maternal T regulatory cell response that contributes to tolerance. Proc Natl Acad Sci U S A 2010;107:9299-9304.
  14. Soares MJ, Varberg KM, Iqbal K. Hemochorial placentation: development, function, and adaptations. Biol Reprod 2018;99:196-211.
  15. Tetro N, Moushaev S, Rubinchik-Stern M, Eyal S. The placental barrier: the gate and the fate in drug distribution. Pharm Res 2018;35:71.
  16. Billington WD, Kirby DRS, Owen JJT, Ritter MA, Burtonshaw MD, Evans EP, Ford CE, Gauld IK, McLaren A. Placental barrier to maternal cells. Nature 1969;224:704-706.
  17. Tuffrey M, Bishun NP, Barnes RD. Porosity of the mouse placenta to maternal cells. Nature 1969;221:1029-1030.
  18. Hunziker RD, Gambel P, Wegmann TG. Placenta as a selective barrier to cellular traffic. J Immunol 1984;133:667-671.
  19. Zhou L, Yoshimura Y, Huang Y, Suzuki R, Yokoyama M, Okabe M, Shimamura M. Two independent pathways of maternal cell transmission to offspring: through placenta during pregnancy and by breastfeeding after birth. Immunology 2000;101:570-580.
  20. Sargent IL, Arenas J, Redman CW. Maternal cell-mediated sensitisation to paternal HLA may occur, but is not a regular event in normal human pregnancy. J Reprod Immunol 1987;10:111-120.
  21. Wegmann TG, Waters CA, Drell DW, Carlson GA. Pregnant mice are not primed but can be primed to fetal alloantigens. Proc Natl Acad Sci U S A 1979;76:2410-2414.
  22. Saito M, Nakashima I, Mizoguchi K, Isobe K, Nagase F, Goto S, Tomoda Y. Immune reactivity of allogeneically pregnant mice to paternal MHC antigens on fetal and placental cells assessed by second set rejection of ascites tumor cells. J Reprod Immunol 1985;8:139-151.
  23. Wegmann TG, Singh B, Carlson GA. Allogeneic placenta is a paternal strain antigen immunoabsorbent. J Immunol 1979;122:270-274.
  24. Wegmann TG, Mosmann TR, Carlson GA, Olijnyk O, Singh B. The ability of the murine placenta to absorb monoclonal anti-fetal H-2K antibody from the maternal circulation. J Immunol 1979;123:1020-1023.
  25. Ishii M, Hayakawa S, Suzuki MK, Yoshino N, Honda M, Nishinarita S, Chishima F, Nagaishi M, Satoh K. Expression of functional chemokine receptors of human placental cells. Am J Reprod Immunol 2000;44:365-373.
  26. Martinez de la Torre Y, Buracchi C, Borroni EM, Dupor J, Bonecchi R, Nebuloni M, Pasqualini F, Doni A, Lauri E, Agostinis C, et al. Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6. Proc Natl Acad Sci U S A 2007;104:2319-2324.
  27. Teoh PJ, Menzies FM, Hansell CA, Clarke M, Waddell C, Burton GJ, Nelson SM, Nibbs RJ. Atypical chemokine receptor ACKR2 mediates chemokine scavenging by primary human trophoblasts and can regulate fetal growth, placental structure, and neonatal mortality in mice. J Immunol 2014;193:5218-5228.
  28. Lee KM, Wilson GJ, Pingen M, Fukuoka A, Hansell CAH, Bartolini R, Medina-Ruiz L, Graham GJ. Placental chemokine compartmentalisation: a novel mammalian molecular control mechanism. PLoS Biol 2019;17:e3000287.
  29. Nancy P, Tagliani E, Tay CS, Asp P, Levy DE, Erlebacher A. Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface. Science 2012;336:1317-1321.
  30. Tersigni C, Di Nicuolo F, Maulucci G, Rolfo A, Giuffrida D, Veglia M, De Spirito M, Scambia G, Todros T, Di Simone N. Placental chemokine receptor D6 is functionally impaired in pre-eclampsia. PLoS One 2016;11:e0164747.
  31. Usta A, Turan G, Sancakli Usta C, Avci E, Adali E. Placental fractalkine immunoreactivity in preeclampsia and its correlation with histopathological changes in the placenta and adverse pregnancy outcomes. J Matern Fetal Neonatal Med 2020;33:806-815.
  32. Neefjes J, Jongsma ML, Paul P, Bakke O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol 2011;11:823-836.
  33. Afzali B, Lombardi G, Lechler RI. Pathways of major histocompatibility complex allorecognition. Curr Opin Organ Transplant 2008;13:438-444.
  34. Wei XH, Orr HT. Differential expression of HLA-E, HLA-F, and HLA-G transcripts in human tissue. Hum Immunol 1990;29:131-142.
  35. Redline RW, Lu CY. Localization of fetal major histocompatibility complex antigens and maternal leukocytes in murine placenta. Implications for maternal-fetal immunological relationship. Lab Invest 1989;61:27-36.
  36. Apps R, Gardner L, Sharkey AM, Holmes N, Moffett A. A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen-presenting cells via LILRB1. Eur J Immunol 2007;37:1924-1937.
  37. Ristich V, Liang S, Zhang W, Wu J, Horuzsko A. Tolerization of dendritic cells by HLA-G. Eur J Immunol 2005;35:1133-1142.
  38. Faure M, Long EO. KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential. J Immunol 2002;168:6208-6214.
  39. Sharkey AM, Gardner L, Hiby S, Farrell L, Apps R, Masters L, Goodridge J, Lathbury L, Stewart CA, Verma S, et al. Killer Ig-like receptor expression in uterine NK cells is biased toward recognition of HLA-C and alters with gestational age. J Immunol 2008;181:39-46.
  40. Hiby SE, Apps R, Sharkey AM, Farrell LE, Gardner L, Mulder A, Claas FH, Walker JJ, Redman CW, Morgan L, et al. Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2. J Clin Invest 2010;120:4102-4110.
  41. Li Q, Meissner TB, Wang F, Du Z, Ma S, Kshirsagar S, Tilburgs T, Buenrostro JD, Uesugi M, Strominger JL. ELF3 activated by a superenhancer and an autoregulatory feedback loop is required for high-level HLA-C expression on extravillous trophoblasts. Proc Natl Acad Sci U S A 2021;118:e2025512118.
  42. Yie SM, Li LH, Li YM, Librach C. HLA-G protein concentrations in maternal serum and placental tissue are decreased in preeclampsia. Am J Obstet Gynecol 2004;191:525-529.
  43. Wang Q, Li J, Wang S, Deng Q, An Y, Xing Y, Dai X, Li Z, Ma Q, Wang K, et al. Single-cell transcriptional profiling reveals cellular and molecular divergence in human maternal-fetal interface. Sci Rep 2022;12:10892.
  44. Murphy SP, Tomasi TB. Absence of MHC class II antigen expression in trophoblast cells results from a lack of class II transactivator (CIITA) gene expression. Mol Reprod Dev 1998;51:1-12.
  45. van den Elsen PJ, van der Stoep N, Vietor HE, Wilson L, van Zutphen M, Gobin SJ. Lack of CIITA expression is central to the absence of antigen presentation functions of trophoblast cells and is caused by methylation of the IFN-γ inducible promoter (PIV) of CIITA. Hum Immunol 2000;61:850-862.
  46. Holtz R, Choi JC, Petroff MG, Piskurich JF, Murphy SP. Class II transactivator (CIITA) promoter methylation does not correlate with silencing of CIITA transcription in trophoblasts. Biol Reprod 2003;69:915-924.
  47. Athanassakis-Vassiliadis I, Galanopoulos VK, Grigoriou M, Papamatheakis J. Induction of class II MHC antigen expression on the murine placenta by 5-azacytidine correlates with fetal abortion. Cell Immunol 1990;128:438-449.
  48. Shima T, Nakashima A, Yasuda I, Ushijima A, Inada K, Tsuda S, Yoshino O, Tomura M, Saito S. Uterine CD11c+ cells induce the development of paternal antigen-specific Tregs via seminal plasma priming. J Reprod Immunol 2020;141:103165.
  49. Collins MK, Tay CS, Erlebacher A. Dendritic cell entrapment within the pregnant uterus inhibits immune surveillance of the maternal/fetal interface in mice. J Clin Invest 2009;119:2062-2073.
  50. Einenkel R, Ehrhardt J, Hartmann K, Kruger D, Muzzio DO, Zygmunt M. Hormonally controlled ILC antigen presentation potential is reduced during pregnancy. Reproduction 2020;160:155-169.
  51. Bulmer JN, Morrison L, Longfellow M, Ritson A, Pace D. Granulated lymphocytes in human endometrium: histochemical and immunohistochemical studies. Hum Reprod 1991;6:791-798.
  52. Han M, Hu L, Wu D, Zhang Y, Li P, Zhao X, Zeng Y, Ren G, Hou Z, Pang Y, et al. IL-21R-STAT3 signalling initiates a differentiation program in uterine tissue-resident NK cells to support pregnancy. Nat Commun 2023;14:7109.
  53. Koopman LA, Kopcow HD, Rybalov B, Boyson JE, Orange JS, Schatz F, Masch R, Lockwood CJ, Schachter AD, Park PJ, et al. Human decidual natural killer cells are a unique NK cell subset with immunomodulatory potential. J Exp Med 2003;198:1201-1212.
  54. Pende D, Sivori S, Accame L, Pareti L, Falco M, Geraghty D, Le Bouteiller P, Moretta L, Moretta A. HLA-G recognition by human natural killer cells. Involvement of CD94 both as inhibitory and as activating receptor complex. Eur J Immunol 1997;27:1875-1880.
  55. Tayade C, Fang Y, Black GP, v A P Jr, Erlebacher A, Croy BA. Differential transcription of Eomes and T-bet during maturation of mouse uterine natural killer cells. J Leukoc Biol 2005;78:1347-1355.
  56. Soderstrom K, Corliss B, Lanier LL, Phillips JH. CD94/NKG2 is the predominant inhibitory receptor involved in recognition of HLA-G by decidual and peripheral blood NK cells. J Immunol 1997;159:1072-1075.
  57. Rajagopalan S, Long EO. A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells. J Exp Med 1999;189:1093-1100.
  58. Colonna M, Navarro F, Bellon T, Llano M, Garcia P, Samaridis J, Angman L, Cella M, Lopez-Botet M. A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells. J Exp Med 1997;186:1809-1818.
  59. Clark MM, Chazara O, Sobel EM, Gjessing HK, Magnus P, Moffett A, Sinsheimer JS. Human birth weight and reproductive immunology: Testing for interactions between maternal and offspring KIR and HLA-C genes. Hum Hered 2016;81:181-193.
  60. Xiong S, Sharkey AM, Kennedy PR, Gardner L, Farrell LE, Chazara O, Bauer J, Hiby SE, Colucci F, Moffett A. Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation. J Clin Invest 2013;123:4264-4272.
  61. Fu B, Li X, Sun R, Tong X, Ling B, Tian Z, Wei H. Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface. Proc Natl Acad Sci U S A 2013;110:E231-E240.
  62. Rowe JH, Ertelt JM, Xin L, Way SS. Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature 2012;490:102-106.
  63. Aluvihare VR, Kallikourdis M, Betz AG. Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 2004;5:266-271.
  64. Samstein RM, Josefowicz SZ, Arvey A, Treuting PM, Rudensky AY. Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict. Cell 2012;150:29-38.
  65. Lee JB, Kim HR, Ha SJ. Immune checkpoint inhibitors in 10 years: contribution of basic research and clinical application in cancer immunotherapy. Immune Netw 2022;22:e2.
  66. Tekguc M, Wing JB, Osaki M, Long J, Sakaguchi S. Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells. Proc Natl Acad Sci U S A 2021;118:e2023739118.
  67. Gianchecchi E, Fierabracci A. Inhibitory receptors and pathways of lymphocytes: The role of PD-1 in Treg development and their involvement in autoimmunity onset and cancer progression. Front Immunol 2018;9:2374.
  68. Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Levitsky HI, et al. Role of LAG-3 in regulatory T cells. Immunity 2004;21:503-513.
  69. Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N, Mak TW, Sakaguchi S. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 2000;192:303-310.
  70. Lee GR. Molecular mechanisms of T helper cell differentiation and functional specialization. Immune Netw 2023;23:e4.
  71. Raimondi G, Shufesky WJ, Tokita D, Morelli AE, Thomson AW. Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ resting regulatory T cells from activated T cells. J Immunol 2006;176:2808-2816.
  72. Sasaki Y, Sakai M, Miyazaki S, Higuma S, Shiozaki A, Saito S. Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod 2004;10:347-353.
  73. Meggyes M, Miko E, Szigeti B, Farkas N, Szereday L. The importance of the PD-1/PD-L1 pathway at the maternal-fetal interface. BMC Pregnancy Childbirth 2019;19:74.
  74. Oida T, Xu L, Weiner HL, Kitani A, Strober W. TGF-β-mediated suppression by CD4+CD25+ T cells is facilitated by CTLA-4 signaling. J Immunol 2006;177:2331-2339.
  75. Lin Y, Liu X, Shan B, Wu J, Sharma S, Sun Y. Prevention of CpG-induced pregnancy disruption by adoptive transfer of in vitro-induced regulatory T cells. PLoS One 2014;9:e94702.
  76. Oliver MA, Davis XD, Bohannon JK. TGFβ macrophage reprogramming: a new dimension of macrophage plasticity. J Leukoc Biol 2024;115:411-414.
  77. Hsu P, Santner-Nanan B, Hu M, Skarratt K, Lee CH, Stormon M, Wong M, Fuller SJ, Nanan R. IL-10 potentiates differentiation of human induced regulatory T cells via STAT3 and Foxo1. J Immunol 2015;195:3665-3674.
  78. Arruvito L, Sanz M, Banham AH, Fainboim L. Expansion of CD4+CD25+and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: implications for human reproduction. J Immunol 2007;178:2572-2578.
  79. Geng X, Mao G, Zhao D, Xiang Y, Wang M, Yu G, Tan L. Downregulation of miR-33a/b and miR-181a contributes to recurrent pregnancy loss by upregulating S1PR1 and repressing regulatory T cell differentiation. Placenta 2022;121:137-144.
  80. Cai S, Dai S, Lin R, Huang C, Zeng Y, Diao L, Lian R, Tu W. The effectiveness and safety of intrauterine infusion of autologous regulatory T cells (Tregs) in patients with recurrent pregnancy loss and low levels of endometrial FoxP3+ cells: a retrospective cohort study. Am J Reprod Immunol 2023;90:e13735.
  81. Shepard MT, Bonney EA. PD-1 regulates T cell proliferation in a tissue and subset-specific manner during normal mouse pregnancy. Immunol Invest 2013;42:385-408.
  82. Wang SC, Li YH, Piao HL, Hong XW, Zhang D, Xu YY, Tao Y, Wang Y, Yuan MM, Li DJ, et al. PD-1 and Tim-3 pathways are associated with regulatory CD8+ T-cell function in decidua and maintenance of normal pregnancy. Cell Death Dis 2015;6:e1738.
  83. Vento-Tormo R, Efremova M, Botting RA, Turco MY, Vento-Tormo M, Meyer KB, Park JE, Stephenson E, Polanski K, Goncalves A, et al. Single-cell reconstruction of the early maternal-fetal interface in humans. Nature 2018;563:347-353.
  84. Wang S, Liu Y, Liang Y, Sun L, Du X, Shi Y, Meng J. Excessive immune activation and the correlation with decreased expression of PD-1 at the maternal-fetal interface in preeclampsia. Reprod Sci 2023;30:192-202.
  85. Jin LP, Chen QY, Zhang T, Guo PF, Li DJ. The CD4+CD25 bright regulatory T cells and CTLA-4 expression in peripheral and decidual lymphocytes are down-regulated in human miscarriage. Clin Immunol 2009;133:402-410.
  86. Whyte A, Loke YW. Increased sialylation of surface glycopeptides of human trophoblast compared with fetal cells from the same conceptus. J Exp Med 1978;148:1087-1092.
  87. Chen Q, Pang PC, Cohen ME, Longtine MS, Schust DJ, Haslam SM, Blois SM, Dell A, Clark GF. Evidence for differential glycosylation of trophoblast cell types. Mol Cell Proteomics 2016;15:1857-1866.
  88. Abeln M, Albers I, Peters-Bernard U, Flachsig-Schulz K, Kats E, Kispert A, Tomlinson S, Gerardy-Schahn R, Munster-Kuhnel A, Weinhold B. Sialic acid is a critical fetal defense against maternal complement attack. J Clin Invest 2019;129:422-436.
  89. Rizzuto G, Brooks JF, Tuomivaara ST, McIntyre TI, Ma S, Rideaux D, Zikherman J, Fisher SJ, Erlebacher A. Establishment of fetomaternal tolerance through glycan-mediated B cell suppression. Nature 2022;603:497-502.
  90. Vijayan M, Lee CL, Wong VHH, Wang X, Bai K, Wu J, Koistinen H, Seppala M, Lee KF, Yeung WSB, et al. Decidual glycodelin-A polarizes human monocytes into a decidual macrophage-like phenotype through Siglec-7. J Cell Sci 2020;133:jcs244400.
  91. Hwu P, Du MX, Lapointe R, Do M, Taylor MW, Young HA. Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J Immunol 2000;164:3596-3599.
  92. Fallarino F, Grohmann U, You S, McGrath BC, Cavener DR, Vacca C, Orabona C, Bianchi R, Belladonna ML, Volpi C, et al. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 2006;176:6752-6761.
  93. Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol 2010;185:3190-3198.
  94. Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, Brown C, Mellor AL. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 1998;281:1191-1193.
  95. Kudo Y, Boyd CAR, Spyropoulou I, Redman CWG, Takikawa O, Katsuki T, Hara T, Ohama K, Sargent IL. Indoleamine 2,3-dioxygenase: distribution and function in the developing human placenta. J Reprod Immunol 2004;61:87-98.
  96. Honig A, Rieger L, Kapp M, Sutterlin M, Dietl J, Kammerer U. Indoleamine 2,3-dioxygenase (IDO) expression in invasive extravillous trophoblast supports role of the enzyme for materno-fetal tolerance. J Reprod Immunol 2004;61:79-86.
  97. Baban B, Chandler P, McCool D, Marshall B, Munn DH, Mellor AL. Indoleamine 2,3-dioxygenase expression is restricted to fetal trophoblast giant cells during murine gestation and is maternal genome specific. J Reprod Immunol 2004;61:67-77.
  98. Lee JH, Ulrich B, Cho J, Park J, Kim CH. Progesterone promotes differentiation of human cord blood fetal T cells into T regulatory cells but suppresses their differentiation into Th17 cells. J Immunol 2011;187:1778-1787.
  99. Fu B, Tian Z, Wei H. TH17 cells in human recurrent pregnancy loss and pre-eclampsia. Cell Mol Immunol 2014;11:564-570.
  100. Wang F, Ferreira LMR, Mazzanti A, Yu H, Gu B, Meissner TB, Li Q, Strominger JL. Progesterone-mediated remodeling of the maternal-fetal interface by a PGRMC1-dependent mechanism. J Reprod Immunol 2024;163:104244.
  101. Schumacher A, Zenclussen AC. Human chorionic gonadotropin-mediated immune responses that facilitate embryo implantation and placentation. Front Immunol 2019;10:2896.
  102. Zhu JY, Pang ZJ, Yu YH. Regulation of trophoblast invasion: the role of matrix metalloproteinases. Rev Obstet Gynecol 2012;5:e137-e143.
  103. Quintero-Fabian S, Arreola R, Becerril-Villanueva E, Torres-Romero JC, Arana-Argaez V, Lara-Riegos J, Ramirez-Camacho MA, Alvarez-Sanchez ME. Role of matrix metalloproteinases in angiogenesis and cancer. Front Oncol 2019;9:1370.
  104. Matjila M, Millar R, van der Spuy Z, Katz A. The differential expression of Kiss1, MMP9 and angiogenic regulators across the feto-maternal interface of healthy human pregnancies: implications for trophoblast invasion and vessel development. PLoS One 2013;8:e63574.
  105. Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2002;2:795-803.
  106. Wang J, Lu Q, Chen X, Aifantis I. Targeting MHC-I inhibitory pathways for cancer immunotherapy. Trends Immunol 2024;45:177-187.
  107. Tanaka A, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Cell Res 2017;27:109-118.
  108. Crosley EJ, Elliot MG, Christians JK, Crespi BJ. Placental invasion, preeclampsia risk and adaptive molecular evolution at the origin of the great apes: evidence from genome-wide analyses. Placenta 2013;34:127-132.
  109. Kshitiz AJ, Afzal J, Maziarz JD, Hamidzadeh A, Liang C, Erkenbrack EM, Kim HN, Haeger JD, Pfarrer C, Hoang T, et al. Evolution of placental invasion and cancer metastasis are causally linked. Nat Ecol Evol 2019;3:1743-1753.
  110. Sivori S, Della Chiesa M, Carlomagno S, Quatrini L, Munari E, Vacca P, Tumino N, Mariotti FR, Mingari MC, Pende D, et al. Inhibitory receptors and checkpoints in human NK cells, implications for the immunotherapy of cancer. Front Immunol 2020;11:2156.
  111. Liu M, Wang X, Wang L, Ma X, Gong Z, Zhang S, Li Y. Targeting the IDO1 pathway in cancer: from bench to bedside. J Hematol Oncol 2018;11:100.