Tumour-infiltrating FOXP3 + lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer

British Journal of Cancer

Volumn 108, Issue 1, 2013, Pages 155-162

  West, N R ^a,b   Kost, S E ^a,b   Martin, S D ^a,c   Milne, K ^a   Deleeuw, R J ^a   Nelson, B H ^a,b,c   Watson, P H ^a,b,c  

^a BRITISH COLUMBIA CANCER AGENCY   (Canada)

^b UNIVERSITY OF VICTORIA   (Canada)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

FOXP3; oestrogen receptor; prognosis; Treg; tumour immunity breast cancer

Indexed keywords

TRANSCRIPTION FACTOR FOXP3;

ARTICLE; BREAST CANCER; CANCER PROGNOSIS; CD4+ CD25+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CYTOTOXICITY; ESTROGEN RECEPTOR NEGATIVE BREAST CANCER; GENE EXPRESSION; HUMAN; IMMUNE RESPONSE; IMMUNOHISTOCHEMISTRY; MAJOR CLINICAL STUDY; OUTCOME ASSESSMENT; PHENOTYPE; PRIORITY JOURNAL; RECURRENCE FREE SURVIVAL; REGULATORY T LYMPHOCYTE; TUMOR ASSOCIATED LEUKOCYTE; TUMOR IMMUNITY;

BREAST NEOPLASMS; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; LYMPHOCYTES, TUMOR-INFILTRATING; MIDDLE AGED; PROGNOSIS; T-LYMPHOCYTES, CYTOTOXIC; TISSUE ARRAY ANALYSIS;

EID: 84872608638     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/bjc.2012.524     Document Type: Article

References (47)

1. Allan SE, Crome SQ, Crellin NK, Passerini L, Steiner TS, Bacchetta R, Roncarolo MG, Levings MK (2007) Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int Immunol 19(4): 345-354.
2. Aruga T, Suzuki E, Saji S, Horiguchi S, Horiguchi K, Sekine S, Kitagawa D, Funata N, Toi M, Sugihara K, Kuroi K (2009) A low number of tumour-infiltrating FOXP3-positive cells during primary systemic chemotherapy correlates with favourable anti-tumour response in patients with breast cancer. Oncol Rep 22(2): 273-278.
3. Baker K, Lachapelle J, Zlobec I, Bismar TA, Terracciano L, Foulkes WD (2011) Prognostic significance of CD8 + T lymphocytes in breast cancer depends upon both oestrogen receptor status and histological grade. Histopathology 58(7): 1107-1116.
4. Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL, Banham AH (2006) Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 24(34): 5373-5380.
5. Blatner NR, Bonertz A, Beckhove P, Cheon EC, Krantz SB, Strouch M, Weitz J, Koch M, Halverson AL, Bentrem DJ, Khazaie K (2010) In colourectal cancer mast cells contribute to systemic regulatory T-cell dysfunction. Proc Natl Acad Sci USA 107(14): 6430-6435.
6. Bohling SD, Allison KH (2008) Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target. Mod Pathol 21(12): 1527-1532.
7. Calabro A, Beissbarth T, Kuner R, Stojanov M, Benner A, Asslaber M, Ploner F, Zatloukal K, Samonigg H, Poustka A, Sultmann H (2009) Effects of infiltrating lymphocytes and oestrogen receptor on gene expression and prognosis in breast cancer. Breast Cancer Res Treat 116(1): 69-77.
8. Camp RL, Dolled-Filhart M, Rimm DL (2004) X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 10(21): 7252-7259.
9. Campbell DJ, Ziegler SF (2007) FOXP3 modifies the phenotypic and functional properties of regulatory T cells. Nat Rev Immunol 7(4): 305-310.
10. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10(9): 942-949.
11. de Kruijf EM, van Nes JG, Sajet A, Tummers QR, Putter H, Osanto S, Speetjens FM, Smit VT, Liefers GJ, van de Velde CJ, Kuppen PJ (2010) The predictive value of HLA class I tumour cell expression and presence of intratumoural Tregs for chemotherapy in patients with early breast cancer. Clin Cancer Res 16(4): 1272-1280.
12. deLeeuw RJ, Kost SE, Kakal JA, Nelson BH (2012) The prognostic value of FoxP3 + tumour-infiltrating lymphocytes in cancer: a critical review of the literature. Clin Cancer Res 18(11): 3022-3029.
13. DeNardo DG, Johansson M, Coussens LM (2008) Immune cells as mediators of solid tumour metastasis. Cancer Metastasis Rev 27(1): 11-18.
14. Desmedt C, Haibe-Kains B, Wirapati P, Buyse M, Larsimont D, Bontempi G, Delorenzi M, Piccart M, Sotiriou C (2008) Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res 14(16): 5158-5165.
15. Ding Y, Xu J, Bromberg JS (2012) Regulatory T cell migration during an immune response. Trends Immunol 33(4): 174-180.
16. Fisher DT, Chen Q, Appenheimer MM, Skitzki J, Wang WC, Odunsi K, Evans SS (2006) Hurdles to lymphocyte trafficking in the tumour microenvironment: implications for effective immunotherapy. Immunol Invest 35(3-4): 251-277.
17. Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. N Engl J Med 363(20): 1938-1948.
18. Frey DM, Droeser RA, Viehl CT, Zlobec I, Lugli A, Zingg U, Oertli D, Kettelhack C, Terracciano L, Tornillo L (2010) High frequency of tumour-infiltrating FOXP3(+) regulatory T cells predicts improved survival in mismatch repair-proficient colourectal cancer patients. Int J Cancer 126(11): 2635-2643.
19. Ghebeh H, Barhoush E, Tulbah A, Elkum N, Al-Tweigeri T, Dermime S (2008) FOXP3 + Tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumour tissues of high-risk breast cancer patients: Implication for immunotherapy. BMC Cancer 8: 57.
20. Gobert M, Treilleux I, Bendriss-Vermare N, Bachelot T, Goddard-Leon S, Arfi V, Biota C, Doffin AC, Durand I, Olive D, Perez S, Pasqual N, Faure C, Ray-Coquard I, Puisieux A, Caux C, Blay JY, Menetrier-Caux C (2009) Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumours and lead to an adverse clinical outcome. Cancer Res 69(5): 2000-2009.
21. Hirahara K, Liu L, Clark RA, Yamanaka K, Fuhlbrigge RC, Kupper TS (2006) The majority of human peripheral blood CD4 + CD25highFoxp3 + regulatory T cells bear functional skin-homing receptors. J Immunol 177(7): 4488-4494.
22. Ladoire S, Mignot G, Dabakuyo S, Arnould L, Apetoh L, Rebe C, Coudert B, Martin F, Bizollon MH, Vanoli A, Coutant C, Fumoleau P, Bonnetain F, Ghiringhelli F (2011) In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival. J Pathol 224(3): 389-400.
23. Ley K, Laudanna C, Cybulsky MI, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7(9): 678-689.
24. Liu F, Lang R, Zhao J, Zhang X, Pringle GA, Fan Y, Yin D, Gu F, Yao Z, Fu L (2011) CD8 (+) cytotoxic T cell and FOXP3(+) regulatory T cell infiltration in relation to breast cancer survival and molecular subtypes. Breast Cancer Res Treat 130(2): 645-655.
25. Liu S, Lachapelle J, Leung S, Gao D, Foulkes WD, Nielsen TO (2012) CD8 + lymphocyte infiltration is an independent favourable prognostic indicator in basal-like breast cancer. Breast Cancer Res 14(2): R48.
26. Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, Ellis IO, Green AR (2011a) Tumour-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol 29(15): 1949-1955.
27. Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Lee AH, Ellis IO, Green AR (2011b) An evaluation of the clinical significance of FOXP3 + infiltrating cells in human breast cancer. Breast Cancer Res Treat 127(1): 99-108.
28. Mantovani A, Bonecchi R, Locati M (2006) Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nat Rev Immunol 6(12): 907-918.
29. Martinet L, Garrido I, Filleron T, Le Guellec S, Bellard E, Fournie JJ, Rochaix P, Girard JP (2011) Human solid tumours contain high endothelial venules: association with T-and B-lymphocyte infiltration and favourable prognosis in breast cancer. Cancer Res 71(17): 5678-5687.
30. Merlo A, Casalini P, Carcangiu ML, Malventano C, Triulzi T, Menard S, Tagliabue E, Balsari A (2009) FOXP3 expression and overall survival in breast cancer. J Clin Oncol 27(11): 1746-1752.
31. Milne K, Kobel M, Kalloger SE, Barnes RO, Gao D, Gilks CB, Watson PH, Nelson BH (2009) Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS ONE 4(7): e6412.
32. Ohmichi Y, Hirakawa J, Imai Y, Fukuda M, Kawashima H (2011) Essential role of peripheral node addressin in lymphocyte homing to nasal-associated lymphoid tissues and allergic immune responses. J Exp Med 208(5): 1015-1025.
33. Oldham KA, Parsonage G, Bhatt RI, Wallace DM, Deshmukh N, Chaudhri S, Adams DH, Lee SP (2012) T lymphocyte recruitment into renal cell carcinoma tissue: a role for chemokine receptors CXCR3, CXCR6, CCR5, and CCR6. Eur Urol 61(2): 385-394.
34. Pages F, Galon J, Dieu-Nosjean MC, Tartour E, Sautes-Fridman C, Fridman WH (2010) Immune infiltration in human tumours: a prognostic factor that should not be ignored. Oncogene 29(8): 1093-1102.
35. Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X, Perou CM (2010) Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 12(5): R68.
36. Redjimi N, Raffin C, Raimbaud I, Pignon P, Matsuzaki J, Odunsi K, Valmori D, Ayyoub M (2012) CXCR3+ T regulatory cells selectively accumulate in human ovarian carcinomas to limit type I immunity. Cancer Res 72(17): 4351-4360.
37. Rody A, Holtrich U, Pusztai L, Liedtke C, Gaetje R, Ruckhaeberle E, Solbach C, Hanker L, Ahr A, Metzler D, Engels K, Karn T, Kaufmann M (2009) T-cell metagene predicts a favourable prognosis in oestrogen receptor-negative and HER2-positive breast cancers. Breast Cancer Res 11(2): R15.
38. Sakaguchi S, Yamaguchi T, Nomura T, Ono M (2008) Regulatory T cells and immune tolerance. Cell 133(5): 775-787.
39. Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, Platell C, Iacopetta B (2009) Tumour-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colourectal cancer. J Clin Oncol 27(2): 186-192.
40. Schmidt M, Bohm D, von Torne C, Steiner E, Puhl A, Pilch H, Lehr HA, Hengstler JG, Kolbl H, Gehrmann M (2008) The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res 68(13): 5405-5413.
41. Shevach EM (2009) Mechanisms of foxp3 + T regulatory cell-mediated suppression. Immunity 30(5): 636-645.
42. Teschendorff AE, Miremadi A, Pinder SE, Ellis IO, Caldas C (2007) An immune response gene expression module identifies a good prognosis subtype in oestrogen receptor negative breast cancer. Genome Biol 8(8): R157.
43. West NR, Milne K, Truong PT, Macpherson N, Nelson BH, Watson PH (2011a) Tumour-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in oestrogen receptor-negative breast cancer. Breast Cancer Res 13(6): R126.
44. West NR, Panet-Raymond V, Truong PT, Alexander C, Babinszky S, Milne K, Ross LA, Loken S, Watson PH (2011b) Intratumoural immune responses can distinguish new primary and true recurrence types of ipsilateral breast tumour recurrences (IBTR). Breast Cancer (Auckl) 5: 105-115.
45. Yan M, Jene N, Byrne D, Millar EK, O'Toole SA, McNeil CM, Bates GJ, Harris AL, Banham AH, Sutherland RL, Fox SB (2011) Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers. Breast Cancer Res 13(2): R47.
46. Yoon HH, Orrock JM, Foster NR, Sargent DJ, Smyrk TC, Sinicrope FA (2012) Prognostic impact of FoxP3+ regulatory t-cells in relation to CD8 + T lymphocyte density in human colon carcinomas. PLoS ONE 7(8): e42274.
47. Zlobec I, Karamitopoulou E, Terracciano L, Piscuoglio S, Iezzi G, Muraro MG, Spagnoli G, Baker K, Tzankov A, Lugli A (2010) TIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic performance of CD8 in mismatch repair-proficient colourectal cancer. PLoS ONE 5(12): e14282.