Treg-cell depletion promotes chemokine production and accumulation of CXCR3+ conventional T cells in intestinal tumors

European Journal of Immunology

Volumn 45, Issue 6, 2015, Pages 1654-1666

  Akeus, Paulina ^a   Langenes, Veronica ^a   Kristensen, Jonas ^a   von Mentzer, Astrid ^a   Sparwasser, Tim ^b   Raghavan, Sukanya ^a   Quiding Järbrink, Marianne ^a  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

^b INSTITUTE OF INFECTION IMMUNOLOGY   (Germany)

Author keywords

Colorectal cancer; CXCL10; CXCL9; Treg cell

Indexed keywords

CHEMOKINE RECEPTOR CXCR3; CXCL9 CHEMOKINE; GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 17; MUCOSAL ADDRESSIN CELL ADHESION MOLECULE 1; VASCULAR CELL ADHESION MOLECULE 1; APC PROTEIN; CELL ADHESION MOLECULE; CHEMOKINE; CHEMOKINE RECEPTOR; CYTOKINE; MADCAM1 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL CELL CULTURE; ANIMAL EXPERIMENT; ANTIGEN EXPRESSION; ANTIGEN PRESENTING CELL; ARTICLE; CANCER IMMUNOTHERAPY; CD4+ CD25+ T LYMPHOCYTE; CELL PROLIFERATION; COLORECTAL CANCER; CYTOKINE PRODUCTION; IN VITRO STUDY; INTESTINE TUMOR; LYMPHOCYTE MIGRATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; T CELL DEPLETION; TRANSENDOTHELIAL AND TRANSEPITHELIAL MIGRATION; ANIMAL; BIOSYNTHESIS; CHEMOTAXIS; COLORECTAL TUMOR; DISEASE MODEL; FEMALE; IMMUNOLOGY; INTESTINE MUCOSA; LYMPHOCYTE ACTIVATION; LYMPHOCYTE DEPLETION; METABOLISM; PHENOTYPE; T LYMPHOCYTE SUBPOPULATION; TH1 CELL; TUMOR ASSOCIATED LEUKOCYTE;

ADENOMATOUS POLYPOSIS COLI PROTEIN; ANIMALS; CELL ADHESION MOLECULES; CHEMOKINES; CHEMOTAXIS; COLORECTAL NEOPLASMS; CYTOKINES; DISEASE MODELS, ANIMAL; FEMALE; INTESTINAL MUCOSA; LYMPHOCYTE ACTIVATION; LYMPHOCYTE DEPLETION; LYMPHOCYTES, TUMOR-INFILTRATING; MICE; PHENOTYPE; RECEPTORS, CHEMOKINE; RECEPTORS, CXCR3; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY; TH1 CELLS; VASCULAR CELL ADHESION MOLECULE-1;

EID: 84930414012     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201445058     Document Type: Article

References (50)

1. Choong, M. K. and Tsafnat, G., Genetic and epigenetic biomarkers of colorectal cancer. Clin. Gastroenterol. Hepatol. 2012. 10: 9-15.
2. Scholer-Dahirel, A., Schlabach, M. R., Loo, A., Bagdasarian, L., Meyer, R., Guo, R., Woolfenden, S. et al., Maintenance of adenomatous polyposis coli (APC)-mutant colorectal cancer is dependent on Wnt/beta-catenin signaling. PNAS 2011. 108: 17135-17140.
3. Gaspar, C., Cardoso, J., Franken, P., Molenaar, L., Morreau, H., Möslein, G., Sampson, J. et al., Cross-species comparison of human and mouse intestinal polyps reveals conserved mechanisms in adenomatous polyposis coli (APC)-driven tumorigenesis. Am. J. Pathol. 2008. 172: 1363-1380.
4. Fodde, R., Smits, R. and Clevers, H., APC, signal transduction and genetic instability in colorectal cancer. Nat. Rev. 2001. 1: 55-67.
5. Moser, A. R., Pitot, H. C. and Dove, W. F. A., Dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 1990. 247: 322-324.
6. Koudougou, C., Bonneville, M., Matysiak-Budnik, T. and Touchefeu, Y., Antitumoural immunity in colorectal cancer-current and potential future implications in clinical practice. Aliment. Pharmacol. Ther. 2013. 38:3-15.
7. Menon, A. G., Janssen van Rhijn, C. M., Morreau, H., Putter, H., Tollenaar, R. A. E. M, vande Velde, C. J. H, Fleuren, G. J. et al., Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis. Lab. Invest. 2004. 84: 493-501.
8. Tosolini, M., Kirilovsky, A., Mlecnik, B., Fredriksen, T., Mauger, S., Bindea, G., Berger, A. et al., Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, Th2, Treg, Th17) in patients with colorectal cancer. Cancer Res. 2011. 71: 1263-1271.
9. Raghavan, S. and Quiding-Järbrink, M., Regulatory T cells in gastrointestinal tumors. Expert. Rev. Gastroenterol. Hepatol. 2011. 5: 489-501.
10. Wing, K. and Sakaguchi, S., Regulatory T cells exert checks and balances on self-tolerance and autoimmunity. Nat. Immunol. 2009. 11: 7-13.
11. Josefowicz, S. Z., Lu L-F. and Rudensky, A. Y., Regulatory T cells: mechanisms of differentiation and function. Annu. Rev. Immunol. 2012. 30: 531-564.
12. Petersen, R. P., Campa, M. J., Sperlazza, J., Conlon, D., Joshi M-B, Harpole, D. H. and Patz, E. F., Tumor infiltrating Foxp3+ regulatory T cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer 2006. 107: 2866-2872.
13. Fu, J., Xu, D., Liu, Z., Shi, M., Zhao, P., Fu, B., Zhang, Z. et al., Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology 2007. 132: 2328-2339.
14. Ménétrier-Caux, C., Gobert, M. and Caux, C., Differences in tumor regulatory T-cell localization and activation status impact patient outcome. Cancer Res. 2009. 69: 7895-7898.
15. Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., Evdemon-Hogan, M. et al., Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 2004. 10: 942-949.
16. Ling, K. L., Pratap, S. E., Bates, G. J., Singh, B., Mortensen, N. J., George, B. D., Warren, B. F. et al., Increased frequency of regulatory T cells in peripheral blood and tumour infiltrating lymphocytes in colorectal cancer patients. Cancer Immun. 2007. 7: 7.
17. LeGouvello, S., Bastuji-Garin, S., Aloulou, N., Mansour, H., Chaumette M-T, Berrehar, F., Seikour, A. et al., High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas. Gut 2008. 57: 772-779.
18. Michel, S., Benner, A., Tariverdian, M., Wentzensen, N., Hoefler, P., Pommerencke, T., Grabe, N. et al., High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instability. Br. J. Cancer 2008. 99: 1867-1873.
19. Svensson, H., Olofsson, V., Lundin, S., Yakkala, C., Björck, S., Börjesson, L., Gustavsson, B. et al., Accumulation of CCR4+ CTLA-4hi FOXP3+CD25hi regulatory T cells in colon adenocarcinomas correlate to reduced activation of conventional T cells. PloS One 2012. 7: e30695.
20. Akeus, P., Langenes, V., Mentzer von, A., Yrlid, U., Sjöling, Å., Saksena, P., Raghavan, S. et al., Altered chemokine production and accumulation of regulatory T cells in intestinal adenomas of APCMin/+ mice. Cancer Immunol. Immunother. 2014, 63: 807-819.
21. Gounaris, E., Blatner, N. R., Dennis, K., Magnusson, F., Gurish, M. F., Strom, T. B., Beckhove, P. et al., T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis. Cancer Res. 2009. 69: 5490-5497.
22. Frey, D. M., Droeser, R. A., Viehl, C. T., Zlobec, I., Lugli, A., Zingg, U., Oertli, D. et al., High frequency of tumor-infiltrating FOXP3 +regulatory T cells predicts improved survival in mismatch repair-proficient colorectal cancer patients. Int. J. Cancer. 2010. 126: 2635-2643.
23. Salama, P., Phillips, M., Grieu, F., Morris, M., Zeps, N., Joseph, D., Platell, C. et al., Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J. Clin. Oncol. 2009. 27: 186-192.
24. Correale, P., Rotundo, M. S., Del Vecchio, M. T., Remondo, C., Migali, C., Ginanneschi, C., Tsang, K. Y. et al., Regulatory (FoxP3+) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy. J. Immunother. 2010. 33: 435-441.
25. Sinicrope, F. A., Rego, R. L., Ansell, S. M., Knutson, K. L., Foster, N. R. and Sargent, D. J., Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinoma. Gastroenterology 2009. 137: 1270-1279.
26. Blatner, N. R., Mulcahy, M. F., Dennis, K. L., Scholtens, D., Bentrem, D. J., Phillips, J. D., Ham, S. et al., Expression of RORγ{phonetic}t marks a pathogenic regulatory T cell subset in human colon cancer. Sci. Transl. Med. 2012. 4: 164ra159.
27. Bonertz, A., Weitz, J., Pietsch, D-H. K, Rahbari, N. N., Schlude, C., Ge, Y., Juenger, S. et al., Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma. J. Clin. Invest. 2009. 119: 3311-3321.
28. Yaqub, S., Henjum, K., Mahic, M., Jahnsen, F. L., Aandahl, E. M., Bjørnbeth, B. A. and Taskén, K., Regulatory T cells in colorectal cancer patients suppress anti-tumor immune activity in a COX-2 dependent manner. Cancer Immunol. Immunother. 2007. 57: 813-821.
29. Enarsson, K., Lundin, B. S., Johnsson, E., Brezicka, T. and Quiding-Järbrink, M., CD4+CD25high regulatory T cells reduce T cell transendothelial migration in cancer patients. Eur. J. immunol. 2007. 37: 282-291.
30. Lahl, K., Loddenkemper, C., Drouin, C., Freyer, J., Arnason, J., Eberl, G. E. R, Hamann, A. et al., Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J. Exp. Med. 2007. 204: 57-63.
31. Staal, F. J. T. and Sen, J. M., The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesis. Eur. J. immunol. 2008. 38: 1788-1794.
32. Manicassamy, S., Reizis, B., Ravindran, R., Nakaya, H., Salazar-Gonzalez, R. M. and Wang, Y. C., Pulendran B. Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science 2010. 329: 849-853.
33. Enarsson, K., Lundgren, A., Kindlund, B., Hermansson, M., Roncador, G., Banham, A. H., Lundin, B. S. et al., Function and recruitment of mucosal regulatory T cells in human chronic Helicobacter pylori infection and gastric adenocarcinoma. Clin. Immunol. 2006. 121: 358-368.
34. Hindley, J. P., Jones, E., Smart, K., Bridgeman, H., Lauder, S. N., Ondondo, B., Cutting, S. et al., T cell trafficking facilitated by high endothelial venules is required for tumor control after regulatory T cell depletion. Cancer Res. 2012. 72: 5473-5482.
35. Nandi, B., Pai, C., Huang, Q., Prabhala, R. H., Munshi, N. C. and Gold, J. S., CCR6, the sole receptor for the chemokine CCL20, promotes spontaneous intestinal tumorigenesis. PloS One 2014. 9: e97566.
36. Billottet, C., Quemener, C. and Bikfalvi, A., CXCR3, a double-edged sword in tumor progression and angiogenesis. Biochim. Biophys. Acta. 2013. 1836: 287-295.
37. Li, X., Kostareli, E., Suffner, J., Garbi, N. and Hämmerling, G. J., Efficient Treg depletion induces T-cell infiltration and rejection of large tumors. Eur. J. Immunol. 2010. 40: 3325-3335.
38. Teng, M. W. L., Ngiow, S. F., von Scheidt, B., McLaughlin, N., Sparwasser, T. and Smyth, M. J., Conditional regulatory T-cell depletion releases adaptive immunity preventing carcinogenesis and suppressing established tumor growth. Cancer Res. 2010. 70: 7800-7809.
39. Sakaguchi, S., Wing, K., Onishi, Y., Prieto-Martin, P. and Yamaguchi, T., Regulatory T cells: how do they suppress immune responses? Int. Immunol. 2009. 21: 1105-1111.
40. Mlecnik, B., Tosolini, M., Charoentong, P., Kirilovsky, A., Bindea, G., Berger, A., Camus, M. et al., Biomolecular network reconstruction identifies T-cell homing factors associated with survival in colorectal cancer. Gastroenterology 2010. 138: 1429-1440.
41. Zipin-Roitman, A., Meshel, T., Sagi-Assif, O., Shalmon, B., Avivi, C., Pfeffer, R. M., Witz, I. P. et al., CXCL10 promotes invasion-related properties in human colorectal carcinoma cells. Cancer Res. 2007. 67: 3396-3405.
42. Redjimi, N., Raffin, C., Raimbaud, I., Pignon, P., Matsuzaki, J., Odunsi, K., Valmori, D. et al., CXCR3+ T regulatory cells selectively accumulate in human ovarian carcinomas to limit type I immunity. Cancer Res. 2012. 72: 4351-4360.
43. Koch, M. A., Tucker-Heard, G., Perdue, N. R., Killebrew, J. R., Urdahl, K. B., Campbell, D. J., The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat. Immunol. 2009. 10: 595-602.
44. Jiang, Z., Xu, Y. and Cai, S., CXCL10 expression and prognostic significance in stage II and III colorectal cancer. Mol. Biol. Rep. 2009. 37: 3029-3036.
45. Grivennikov, S. I., Wang, K., Mucida, D., Stewart, C. A., Schnabl, B., Jauch, D., Taniguchi, K. et al., Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 2012. 491: 254-258.
46. Chae, W. J., Gibson, T. F., Zelterman, D., Hao, L., Henegariu, O. and Bothwell, A. L. M., Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. PNAS 2010. 107: 5540-5544.
47. Dennis, K. L., Wang, Y., Blatner, N. R., Wang, S., Saadalla, A., Trudeau, E., Roers, A. et al., Adenomatous polyps are driven by microbe-instigated focal inflammation and are controlled by IL-10-producing T cells. Cancer Res. 2013. 73: 5905-5913.
48. Lotti, F., Jarrar, A. M., Pai, R. K., Hitomi, M., Lathia, J., Mace, A., Gantt, G. A. et al., Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A. J. Exp. Med. 2013. 210: 2851-2872.
49. Martin, F., Apetoh, L. and Ghiringhelli F., Controversies on the role of Th17 in cancer: a TGF-β-dependent immunosuppressive activity? Trends Mol. Med. 2012. 18: 742-749.
50. Dietrich, W. F., Lander, E. S., Smith, J. S., Moser, A. R., Gould, K. A., Luongo, C., Borenstein, N. et al., Genetic identification of mom-l, a major modifier locus affecting min-induced intestinal neoplasia in the mouse. Cell 1993. 75: 631-639.