Dynamic Treg interactions with intratumoral APCs promote local CTL dysfunction

Journal of Clinical Investigation

Volumn 124, Issue 6, 2014, Pages 2425-2440

  Bauer, Christian A ^a   Kim, Edward Y ^a   Marangoni, Francesco ^a   Carrizosa, Esteban ^a   Claudio, Natalie M ^a   Mempel, Thorsten R ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APC PROTEIN; MEMBRANE PROTEIN; PROGRAMMED DEATH 1 RECEPTOR; T CELL IMMUNOGLOBULIN MUCIN 3; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL MIGRATION; CELL THERAPY; CYTOKINE RELEASE; CYTOTOXIC T LYMPHOCYTE; MICROSCOPY; MIGRATION; MOUSE; MURINE MODEL; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; TUMOR REJECTION;

ADAPTIVE IMMUNITY; ANIMALS; ANTIGEN-PRESENTING CELLS; ANTIGENS, NEOPLASM; CELL COMMUNICATION; CELL LINE, TUMOR; IMMUNOTHERAPY, ADOPTIVE; LYMPHOCYTES, TUMOR-INFILTRATING; MICE; MICE, INBRED BALB C; MICE, TRANSGENIC; MODELS, IMMUNOLOGICAL; SIGNAL TRANSDUCTION; T-LYMPHOCYTES, CYTOTOXIC; T-LYMPHOCYTES, REGULATORY; TUMOR ESCAPE;

EID: 84902184973     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI66375     Document Type: Article

References (73)

1. + T cells render the tumor environment permissive for infiltration by low-avidity CD8+ T cells. J Immunol. 2008;180(5):3122-3131.
2. Martin-Orozco N, et al. T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity. 2009;31(5):787-798.
3. + T-cell help in the tumor milieu is required for recruitment and cytolytic function of CD8+ T lymphocytes. Cancer Res. 2010;70(21):8368-8377.
4. + T cells. Immunity. 2005;22(3):371-383.
5. Muranski P, et al. Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood. 2008;112(2):362-373.
6. Boon T, Cerottini JC, Van den Eynde B, van der Bruggen P, Van Pel A. Tumor antigens recognized by T lymphocytes. Annu Rev Immunol. 1994;12:337-365.
7. Curiel TJ, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10(9):942-949.
8. Zippelius A, et al. Effector function of human tumor-specific CD8 T cells in melanoma lesions: a state of local functional tolerance. Cancer Res. 2004;64(8):2865-2873.
9. Baitsch L, et al. Exhaustion of tumor-specific CD8 (+) T cells in metastases from melanoma patients. J Clin Invest. 2011;121(6):2350-2360.
10. Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 2010;207(10):2187-2194.
11. + T cell dysfunction in melanoma patients. J Exp Med. 2010;207(10):2175-2186.
12. Ahmadzadeh M, et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009;114(8):1537-1544.
13. Brahmer JR, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455-2465.
14. Topalian SL, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443-2454.
15. Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol. 2012;12(4):269-281.
16. Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol. 2012;30:531-564.
17. + T reg cells. J Exp Med. 2012;209(10):1723-1742.
18. Malchow S, et al. Aire-dependent thymic development of tumor-associated regulatory T cells. Science. 2013;339(6124):1219-1224.
19. Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol. 2008;8(7):523-532.
20. Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12(6):492-499.
21. Klein L, Khazaie K, von Boehmer H. In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitro. Proc Natl Acad Sci U S A. 2003;100(15):8886-8891.
22. Klein L, et al. Visualizing the course of antigenspecific CD8 and CD4 T cell responses to a growing tumor. Eur J Immunol. 2003;33(3):806-814.
23. Agata Y, et al. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol. 1996;8(5):765-772.
24. Honda T, Egen JG, Lämmermann T, Kastenmüller W, Torabi-Parizi P, Germain RN. Tuning of antigen sensitivity by T cell receptor-dependent negative feedback controls T cell effector function in inflamed tissues. Immunity. 2014;40(2):235-247.
25. Morgan DJ, et al. CD8 (+) T cell-mediated spontaneous diabetes in neonatal mice. J Immunol. 1996;157(3):978-983.
26. Chen ML, et al. Regulatory T cells suppress tumorspecific CD8 T cell cytotoxicity through TGF-β signals in vivo. Proc Natl Acad Sci U S A. 2005;102(2):419-424.
27. + regulatory T cell function. Science. 2008;322(5899):271-275.
28. Qureshi OS, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011;332(6029):600-603.
29. + regulatory T cells prevent autoimmunity by inhibiting dendritic cells from activating autoreactive T cells. J Immunol. 2007;179(7):4685-4693.
30. Zhang N, et al. Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response. Immunity. 2009;30(3):458-469.
31. Smigiel KS, et al. CCR7 provides localized access to IL-2 and defines homeostatically distinct regulatory T cell subsets. J Exp Med. 2014;211(1):121-136.
32. Tang Q, et al. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity. 2008;28(5):687-697.
33. Kim HP, Leonard WJ. The basis for TCR-mediated regulation of the IL-2 receptor α chain gene: role of widely separated regulatory elements. EMBO J. 2002;21(12):3051-3059.
34. Malek TR, Castro I. Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity. 2010;33(2):153-165.
35. Wu Y, et al. FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell. 2006;126(2):375-387.
36. Marangoni F, et al. The transcription factor NFAT exhibits signal memory during serial T cell interactions with antigen-presenting cells. Immunity. 2013;38(2):237-249.
37. Khanna KM, Blair DA, Vella AT, McSorley SJ, Datta SK, Lefrancois L. T cell and APC dynamics in situ control the outcome of vaccination. J Immunol. 2010;185(1):239-252.
38. Tang Q, et al. Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat Immunol. 2006;7(1):83-92.
39. + immunoregulatory T cells is antigen nonspecific. J Immunol. 2000;164(1):183-190.
40. Romagnoli P, Hudrisier D, van Meerwijk JP. Preferential recognition of self antigens despite normal thymic deletion of CD4 (+) CD25 (+) regulatory T cells. J Immunol. 2002;168(4):1644-1648.
41. + T cell receptors. Immunity. 2004;21(2):267-277.
42. + regulatory T cells induced by an agonist self-peptide. Nat Immunol. 2001;2(4):301-306.
43. Apostolou I, Sarukhan A, Klein L, von Boehmer H. Origin of regulatory T cells with known specificity for antigen. Nat Immunol. 2002;3(8):756-763.
44. + T cells. J Immunol. 2007;178(11):7032-7041.
45. Kawahata K, et al. Generation of CD4 (+) CD25 (+) regulatory T cells from autoreactive T cells simultaneously with their negative selection in the thymus and from nonautoreactive T cells by endogenous TCR expression. J Immunol. 2002;168(9):4399-4405.
46. Nishikawa H, Sakaguchi S. Regulatory T cells in tumor immunity. Int J Cancer. 2010;127(4):759-767.
47. + regulatory T cells in the steady state. J Exp Med. 2003;198(5):737-746.
48. Darrasse-Jeze G, et al. Tumor emergence is sensed by self-specific CD44hi memory Tregs that create a dominant tolerogenic environment for tumors in mice. J Clin Invest. 2009;119(9):2648-2662.
49. Grinberg-Bleyer Y, et al. Pathogenic T cells have a paradoxical protective effect in murine autoimmune diabetes by boosting Tregs. J Clin Invest. 2010;120(12):4558-4568.
50. O'Gorman WE, et al. The initial phase of an immune response functions to activate regulatory T cells. J Immunol. 2009;183(1):332-339.
51. Sharma MD, et al. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2, 3-dioxygenase. J Clin Invest. 2007;117(9):2570-2582.
52. + T cells secreting interleukin-10 and transforming growth factor-beta1 mediates suppression in the tumor microenvironment. Clin Cancer Res. 2007;13(15 pt 1):4345-4354.
53. Zheng Y, Josefowicz SZ, Kas A, Chu TT, Gavin MA, Rudensky AY. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature. 2007;445(7130):936-940.
54. + T cells. Nat Immunol. 2007;8(12):1353-1362.
55. Mrass P, et al. Random migration precedes stable target cell interactions of tumor-infiltrating T cells. J Exp Med. 2006;203(12):2749-2761.
56. Breart B, Lemaitre F, Celli S, Bousso P. Two-photon imaging of intratumoral CD8 T cell cytotoxic activity during adoptive T cell therapy in mice. J Clin Invest. 2008;118(4):1390-1397.
57. Deguine J, Breart B, Lemaitre F, Di Santo JP, Bousso P. Intravital imaging reveals distinct dynamics for natural killer and CD8 (+) T cells during tumor regression. Immunity. 2010;33(4):632-644.
58. Boissonnas A, Fetler L, Zeelenberg IS, Hugues S, Amigorena S. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor. J Exp Med. 2007;204(2):345-356.
59. Wing JB, Sakaguchi S. Multiple treg suppressive modules and their adaptability. Front Immunol. 2012;3:178.
60. Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13(4):227-242.
61. Dannenmann SR, et al. Tumor-associated macrophages subvert T-cell function and correlate with reduced survival in clear cell renal cell carcinoma. Oncoimmunology. 2013;2(3):e23562.
62. + T cells: when, where, and how. Annu Rev Immunol. 2006;24:519-540.
63. Mempel TR, et al. Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation. Immunity. 2006;25(1):129-141.
64. Kryczek I, et al. Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment. J Immunol. 2007;178(11):6730-6733.
65. Li H, et al. Tim-3/galectin-9 signaling pathway mediates T-cell dysfunction and predicts poor prognosis in patients with hepatitis B virus-associated hepatocellular carcinoma. Hepatology. 2012;56(4):1342-1351.
66. Nakanishi Y, Lu B, Gerard C, Iwasaki A. CD8 (+) T lymphocyte mobilization to virus-infected tissue requires CD4 (+) T-cell help. Nature. 2009;462(7272):510-513.
67. + natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc Natl Acad Sci U S A. 2008;105(29):10113-10118.
68. + single positive cells with a class II major histocompatibility complex-restricted receptor. J Exp Med. 1994;180(1):25-34.
69. Mostoslavsky G, Fabian AJ, Rooney S, Alt FW, Mulligan RC. Complete correction of murine Artemis immunodeficiency by lentiviral vector-mediated gene transfer. Proc Natl Acad Sci U S A. 2006;103(44):16406-16411.
70. Brattain MG, Strobel-Stevens J, Fine D, Webb M, Sarrif AM. Establishment of mouse colonic carcinoma cell lines with different metastatic properties. Cancer Res. 1980;40(7):2142-2146.
71. Alexander S, Koehl GE, Hirschberg M, Geissler EK, Friedl P. Dynamic imaging of cancer growth and invasion: a modified skin-fold chamber model. Histochem Cell Biol. 2008;130(6):1147-1154.
72. Fukumura D, et al. Tumor induction of VEGF promoter activity in stromal cells. Cell. 1998;94(6):715-725.
73. Sumen C, Mempel TR, Mazo IB, Von Andrian UH. Intravital microscopy; visualizing immunity in context. Immunity. 2004;21(3):315-329.