Elevated CD3+ and CD8+ tumor-infiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level

Journal of Neuroimmunology

Volumn 264, Issue 1-2, 2013, Pages 71-83

  Kmiecik, Justyna ^a   Poli, Aurélie ^a,b   Brons, Nicolaas H C ^b   Waha, Andreas ^c   Eide, Geir Egil ^a,d   Enger, Per Øyvind ^d   Zimmer, Jacques ^b   Chekenya, Martha ^a  

^a UNIVERSITY OF BERGEN   (Norway)

^b LUXEMBOURG INSTITUTE OF HEALTH   (Luxembourg)

^c UNIVERSITY HOSPITAL BONN   (Germany)

^d HAUKELAND UNIVERSITY HOSPITAL   (Norway)

Author keywords

Antigen presenting cells; GBM; Regulatory T cells; Tumor infiltrating cells

Indexed keywords

5' NUCLEOTIDASE; CD39 ANTIGEN; CD8 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; INTERLEUKIN 10; METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE; TRANSCRIPTION FACTOR FOXP3;

ADULT; AGED; ARTICLE; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; CD3+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; FEMALE; GLIOBLASTOMA; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOGENICITY; LYMPHOCYTE COUNT; LYMPHOCYTIC INFILTRATION; MAJOR CLINICAL STUDY; MALE; OUTCOME ASSESSMENT; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; REGULATORY T LYMPHOCYTE; SURVIVAL TIME; TUMOR ASSOCIATED LEUKOCYTE; TUMOR ESCAPE; TUMOR IMMUNOLOGY; TUMOR MICROENVIRONMENT; UPREGULATION;

ANTIGEN PRESENTING CELLS; GBM; REGULATORY T CELLS; TUMOR INFILTRATING CELLS;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ANTIGENS, CD; ANTIGENS, CD28; ANTIGENS, CD3; BRAIN NEOPLASMS; CHILD; CTLA-4 ANTIGEN; FEMALE; FOLLOW-UP STUDIES; FORKHEAD TRANSCRIPTION FACTORS; GLIOBLASTOMA; HUMANS; IMMUNOSUPPRESSIVE AGENTS; KAPLAN-MEIER ESTIMATE; LYMPHOCYTES, TUMOR-INFILTRATING; MACROPHAGES; MALE; MICROGLIA; MIDDLE AGED; YOUNG ADULT;

EID: 84886774000     PISSN: 01655728     EISSN: 18728421     Source Type: Journal    
DOI: 10.1016/j.jneuroim.2013.08.013     Document Type: Article

References (64)

1. Alter A., Duddy M., Hebert S., Biernacki K., Prat A., Antel J.P., Yong V.W., Nuttall R.K., Pennington C.J., Edwards D.R., Bar-Or A. Determinants of human B cell migration across brain endothelial cells. J. Immunol. 2003, 170:4497-4505.
2. Bauer S., Groh V., Wu J., Steinle A., Phillips J.H., Lanier L.L., Spies T. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 1999, 285:727-729.
3. Becher B., Prat A., Antel J.P. Brain-immune connection: immuno-regulatory properties of CNS-resident cells. Glia 2000, 29:293-304.
4. Carpentier A.F., Meng Y. Recent advances in immunotherapy for human glioma. Curr. Opin. Oncol. 2006, 18:631-636.
5. Chui C.S., Li D. Role of immunoglobulin-like transcript family receptors and their ligands in suppressor T-cell-induced dendritic cell tolerization. Hum. Immunol. 2009, 70:686-691.
6. Cortesini R. Pancreas cancer and the role of soluble immunoglobulin-like transcript 3 (ILT3). JOP 2007, 8:697-703.
7. Costa B.M., Caeiro C., Guimaraes I., Martinho O., Jaraquemada T., Augusto I., Castro L., Osorio L., Linhares P., Honavar M., Resende M., Braga F., Silva A., Pardal F., Amorim J., Nabico R., Almeida R., Alegria C., Pires M., Pinheiro C., Carvalho E., Lopes J.M., Costa P., Damasceno M., Reis R.M. Prognostic value of MGMT promoter methylation in glioblastoma patients treated with temozolomide-based chemoradiation: a Portuguese multicentre study. Oncol. Rep. 2010, 23:1655-1662.
8. Costello R.T., Sivori S., Mallet F., Sainty D., Arnoulet C., Reviron D., Gastaut J.A., Moretta A., Olive D. A novel mechanism of antitumor response involving the expansion of CD3+/CD56+ large granular lymphocytes triggered by a tumor-expressed activating ligand. Leuk. Off. J. Leuk. Soc. Am. Leuk. Res. Fund UK 2002, 16:855-860.
9. de Visser K.E., Eichten A., Coussens L.M. Paradoxical roles of the immune system during cancer development. Nat. Rev. Cancer 2006, 6:24-37.
10. Diefenbach A., Jamieson A.M., Liu S.D., Shastri N., Raulet D.H. Ligands for the murine NKG2D receptor: expression by tumor cells and activation of NK cells and macrophages. Nat. Immunol. 2000, 1:119-126.
11. Dunn G.P., Dunn I.F., Curry W.T. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human glioma. Cancer Immun. 2007, 7:12.
12. Eissmann P., Evans J.H., Mehrabi M., Rose E.L., Nedvetzki S., Davis D.M. Multiple mechanisms downstream of TLR-4 stimulation allow expression of NKG2D ligands to facilitate macrophage/NK cell crosstalk. J. Immunol. 2010, 184:6901-6909.
13. Fecci P.E., Mitchell D.A., Whitesides J.F., Xie W., Friedman A.H., Archer G.E., Herndon J.E., Bigner D.D., Dranoff G., Sampson J.H. Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res. 2006, 66:3294-3302.
14. Fecci P.E., Ochiai H., Mitchell D.A., Grossi P.M., Sweeney A.E., Archer G.E., Cummings T., Allison J.P., Bigner D.D., Sampson J.H. Systemic CTLA-4 blockade ameliorates glioma-induced changes to the CD4+ T cell compartment without affecting regulatory T-cell function. Clin. Cancer Res. 2007, 13:2158-2167.
15. Filaci G., Fenoglio D., Fravega M., Ansaldo G., Borgonovo G., Traverso P., Villaggio B., Ferrera A., Kunkl A., Rizzi M., Ferrera F., Balestra P., Ghio M., Contini P., Setti M., Olive D., Azzarone B., Carmignani G., Ravetti J.L., Torre G., Indiveri F. CD8+ CD28-T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers. J. Immunol. 2007, 179:4323-4334.
16. Foy T.M., Aruffo A., Bajorath J., Buhlmann J.E., Noelle R.J. Immune regulation by CD40 and its ligand GP39. Annu. Rev. Immunol. 1996, 14:591-617.
17. Garcia P., De Heredia A.B., Bellon T., Carpio E., Llano M., Caparros E., Aparicio P., Lopez-Botet M. Signalling via CD70, a member of the TNF family, regulates T cell functions. J. Leukoc. Biol. 2004, 76:263-270.
18. Gibbings D., Befus A.D. CD4 and CD8: an inside-out coreceptor model for innate immune cells. J. Leukoc. Biol. 2009, 86:251-259.
19. Gomez G.G., Kruse C.A. Mechanisms of malignant glioma immune resistance and sources of immunosuppression. Gene Ther. Mol. Biol. 2006, 10:133-146.
20. Grzywacz B., Kataria N., Verneris M.R. CD56(dim)CD16(+) NK cells downregulate CD16 following target cell induced activation of matrix metalloproteinases. Leukemia 2007, 21:356-359. (author reply 359).
21. Hartigan-O'Connor D.J., Poon C., Sinclair E., McCune J.M. Human CD4+ regulatory T cells express lower levels of the IL-7 receptor alpha chain (CD127), allowing consistent identification and sorting of live cells. J. Immunol. Methods 2007, 319:41-52.
22. Hausler S.F., Montalban del Barrio I., Strohschein J., Anoop Chandran P., Engel J.B., Honig A., Ossadnik M., Horn E., Fischer B., Krockenberger M., Heuer S., Seida A.A., Junker M., Kneitz H., Kloor D., Klotz K.N., Dietl J., Wischhusen J. Ectonucleotidases CD39 and CD73 on OvCA cells are potent adenosine-generating enzymes responsible for adenosine receptor 2A-dependent suppression of T cell function and NK cell cytotoxicity. Cancer Immunol. Immunother.: CII 2011, 60:1405-1418.
23. Hegi M.E., Diserens A.C., Gorlia T., Hamou M.F., de Tribolet N., Weller M., Kros J.M., Hainfellner J.A., Mason W., Mariani L., Bromberg J.E., Hau P., Mirimanoff R.O., Cairncross J.G., Janzer R.C., Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N. Engl. J. Med. 2005, 352:997-1003.
24. Heimberger A.B., Abou-Ghazal M., Reina-Ortiz C., Yang D.S., Sun W., Qiao W., Hiraoka N., Fuller G.N. Incidence and prognostic impact of FoxP3+ regulatory T cells in human gliomas. Clin. Cancer Res. 2008, 14:5166-5172.
25. Hodi F.S., O'Day S.J., McDermott D.F., Weber R.W., Sosman J.A., Haanen J.B., Gonzalez R., Robert C., Schadendorf D., Hassel J.C., Akerley W., van den Eertwegh A.J., Lutzky J., Lorigan P., Vaubel J.M., Linette G.P., Hogg D., Ottensmeier C.H., Lebbe C., Peschel C., Quirt I., Clark J.I., Wolchok J.D., Weber J.S., Tian J., Yellin M.J., Nichol G.M., Hoos A., Urba W.J. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 2010, 363:711-723.
26. Jacobs J.F., Idema A.J., Bol K.F., Grotenhuis J.A., de Vries I.J., Wesseling P., Adema G.J. Prognostic significance and mechanism of Treg infiltration in human brain tumors. J. Neuroimmunol. 2010, 225:195-199.
27. Jeffes E.W., Beamer Y.B., Jacques S., Silberman R.S., Vayuvegula B., Gupta S., Coss J.S., Yamamoto R.S., Granger G.A. Therapy of recurrent high grade gliomas with surgery, and autologous mitogen activated IL-2 stimulated killer (MAK) lymphocytes: I. Enhancement of MAK lytic activity and cytokine production by PHA and clinical use of PHA. J. Neurooncol. 1993, 15:141-155.
28. Jyothi M.D., Khar A. Regulation of CD40L expression on natural killer cells by interleukin-12 and interferon gamma: its role in the elicitation of an effective antitumor immune response. Cancer Immunol. Immunother. 2000, CII 49:563-572.
29. Kaplan E.L., Meier P. Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 1958, 53:457-481.
30. Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern. Med. Rev. 2003, 8:223-246.
31. Kim Y.H., Jung T.Y., Jung S., Jang W.Y., Moon K.S., Kim I.Y., Lee M.C., Lee J.J. Tumour-infiltrating T-cell subpopulations in glioblastomas. Br. J. Neurosurg. 2012, 26:21-27.
32. Kloss M., Decker P., Baltz K.M., Baessler T., Jung G., Rammensee H.G., Steinle A., Krusch M., Salih H.R. Interaction of monocytes with NK cells upon Toll-like receptor-induced expression of the NKG2D ligand MICA. J. Immunol. 2008, 181:6711-6719.
33. Levy E.M., Roberti M.P., Mordoh J. Natural killer cells in human cancer: from biological functions to clinical applications. J. Biomed. Biotechnol. 2011, 2011:676198.
34. Lohr J., Ratliff T., Huppertz A., Ge Y., Dictus C., Ahmadi R., Grau S., Hiraoka N., Eckstein V., Ecker R.C., Korff T., von Deimling A., Unterberg A., Beckhove P., Herold-Mende C. Effector T-cell infiltration positively impacts survival of glioblastoma patients and is impaired by tumor-derived TGF-beta. Clin. Cancer Res. 2011, 17:4296-4308.
35. Louis D.N., Ohgaki H., Wiestler O.D., Cavenee W.K., Burger P.C., Jouvet A., Scheithauer B.W., Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007, 114:97-109.
36. Malmberg K.J., Ljunggren H.G. Escape from immune- and nonimmune-mediated tumor surveillance. Semin. Cancer Biol. 2006, 16:16-31.
37. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother. Rep. 1966, 50:163-170.
38. Mikeska T., Bock C., El-Maarri O., Hubner A., Ehrentraut D., Schramm J., Felsberg J., Kahl P., Buttner R., Pietsch T., Waha A. Optimization of quantitative MGMT promoter methylation analysis using pyrosequencing and combined bisulfite restriction analysis. J. Mol. Diagn. 2007, 9:368-381.
39. Mittelbronn M., Simon P., Loffler C., Capper D., Bunz B., Harter P., Schlaszus H., Schleich A., Tabatabai G., Goeppert B., Meyermann R., Weller M., Wischhusen J. Elevated HLA-E levels in human glioblastomas but not in grade I to III astrocytomas correlate with infiltrating CD8+ cells. J. Neuroimmunol. 2007, 189:50-58.
40. Ostrand-Rosenberg S., Sinha P. Myeloid-derived suppressor cells: linking inflammation and cancer. J. Immunol. 2009, 182:4499-4506.
41. Pittet M.J., Speiser D.E., Valmori D., Cerottini J.C., Romero P. Cutting edge: cytolytic effector function in human circulating CD8+ T cells closely correlates with CD56 surface expression. J. Immunol. 2000, 164:1148-1152.
42. Prendergast C.T., Anderton S.M. Immune cell entry to central nervous system-current understanding and prospective therapeutic targets. Endocr. Metab. Immune Disord. Drug Targets 2009, 9:315-327.
43. Purdy A.K., Campbell K.S. Natural killer cells and cancer: regulation by the killer cell Ig-like receptors (KIR). Cancer Biol. Ther. 2009, 8:2211-2220.
44. Quan N., Herkenham M. Connecting cytokines and brain: a review of current issues. Histol. Histopathol. 2002, 17:273-288.
45. Ribot J.C., Debarros A., Mancio-Silva L., Pamplona A., Silva-Santos B. B7-CD28 costimulatory signals control the survival and proliferation of murine and human gammadelta T cells via IL-2 production. J. Immunol. 2012, 189:1202-1208.
46. Robert C., Thomas L., Bondarenko I., O'Day S., Weber J., Garbe C., Lebbe C., Baurain J.F., Testori A., Grob J.J., Davidson N., Richards J., Maio M., Hauschild A., Miller W.H., Gascon P., Lotem M., Harmankaya K., Ibrahim R., Francis S., Chen T.T., Humphrey R., Hoos A., Wolchok J.D. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N. Engl. J. Med. 2011, 364:2517-2526.
47. Rossi M.L., Jones N.R., Candy E., Nicoll J.A., Compton J.S., Hughes J.T., Esiri M.M., Moss T.H., Cruz-Sanchez F.F., Coakham H.B. The mononuclear cell infiltrate compared with survival in high-grade astrocytomas. Acta Neuropathol. 1989, 78:189-193.
48. Rouas-Freiss N., Moreau P., Ferrone S., Carosella E.D. HLA-G proteins in cancer: do they provide tumor cells with an escape mechanism?. Cancer Res. 2005, 65:10139-10144.
49. Safdari H., Hochberg F.H., Richardson E.P. Prognostic value of round cell (lymphocyte) infiltration in malignant gliomas. Surg. Neurol. 1985, 23:221-226.
50. Sciacca F.L., Ciusani E., Silvani A., Corsini E., Frigerio S., Pogliani S., Parati E., Croci D., Boiardi A., Salmaggi A. Genetic and plasma markers of venous thromboembolism in patients with high grade glioma. Clin. Cancer Res. 2004, 10:1312-1317.
51. Sehgal A., Berger M.S. Basic concepts of immunology and neuroimmunology. Neurosurg. Focus. 2000, 9:e1.
52. Shiroishi M., Tsumoto K., Amano K., Shirakihara Y., Colonna M., Braud V.M., Allan D.S., Makadzange A., Rowland-Jones S., Willcox B., Jones E.Y., van der Merwe P.A., Kumagai I., Maenaka K. Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:8856-8861.
53. Smith-Garvin J.E., Koretzky G.A., Jordan M.S. T cell activation. Annu. Rev. Immunol. 2009, 27:591-619.
54. Sonabend A.M., Rolle C.E., Lesniak M.S. The role of regulatory T cells in malignant glioma. Anticancer. Res. 2008, 28:1143-1150.
55. Stupp R., Mason W.P., van den Bent M.J., Weller M., Fisher B., Taphoorn M.J., Belanger K., Brandes A.A., Marosi C., Bogdahn U., Curschmann J., Janzer R.C., Ludwin S.K., Gorlia T., Allgeier A., Lacombe D., Cairncross J.G., Eisenhauer E., Mirimanoff R.O. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005, 352:987-996.
56. Stupp R., Hegi M.E., Mason W.P., van den Bent M.J., Taphoorn M.J., Janzer R.C., Ludwin S.K., Allgeier A., Fisher B., Belanger K., Hau P., Brandes A.A., Gijtenbeek J., Marosi C., Vecht C.J., Mokhtari K., Wesseling P., Villa S., Eisenhauer E., Gorlia T., Weller M., Lacombe D., Cairncross J.G., Mirimanoff R.O. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009, 10:459-466.
57. Tang J., Flomenberg P., Harshyne L., Kenyon L., Andrews D.W. Glioblastoma patients exhibit circulating tumor-specific CD8+ T cells. Clin. Cancer Res. 2005, 11:5292-5299.
58. Ueda R., Low K.L., Zhu X., Fujita M., Sasaki K., Whiteside T.L., Butterfield L.H., Okada H. Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant glioma. J. Transl. Med. 2007, 5:68.
59. Wang R.F. CD8+ regulatory T cells, their suppressive mechanisms, and regulation in cancer. Hum. Immunol. 2008, 69:811-814.
60. Yang I., Han S.J., Kaur G., Crane C., Parsa A.T. The role of microglia in central nervous system immunity and glioma immunology. J. Clin. Neurosci. 2010, 17:6-10.
61. Yang I., Tihan T., Han S.J., Wrensch M.R., Wiencke J., Sughrue M.E., Parsa A.T. CD8+ T-cell infiltrate in newly diagnosed glioblastoma is associated with long-term survival. J. Clin. Neurosci. 2010, 17:1381-1385.
62. Yang S., Liu F., Wang Q.J., Rosenberg S.A., Morgan R.A. The shedding of CD62L (L-selectin) regulates the acquisition of lytic activity in human tumor reactive T lymphocytes. PLoS One 2011, 6:e22560.
63. Zhang B. CD73: a novel target for cancer immunotherapy. Cancer Res. 2010, 70:6407-6411.
64. Zou J.P., Morford L.A., Chougnet C., Dix A.R., Brooks A.G., Torres N., Shuman J.D., Coligan J.E., Brooks W.H., Roszman T.L., Shearer G.M. Human glioma-induced immunosuppression involves soluble factor(s) that alters monocyte cytokine profile and surface markers. J. Immunol. 1999, 162:4882-4892.