Disrupted fibroblastic reticular cells and interleukin‑7 expression in tumor draining lymph nodes

Gao,Jianbao; Zhao,Lintao; Liu,Lina; Yang,Yang; Guo,Bo; Zhu,Bo

doi:10.3892/ol.2017.6537

Disrupted fibroblastic reticular cells and interleukin‑7 expression in tumor draining lymph nodes

Authors:
- Jianbao Gao
- Lintao Zhao
- Lina Liu
- Yang Yang
- Bo Guo
- Bo Zhu
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Affiliations: Department of Oncology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China
Published online on: July 7, 2017 https://doi.org/10.3892/ol.2017.6537
Pages: 2954-2960
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The immune system of patients with cancer is usually in an inhibitory state. Lymph node (LN) draining of pathological sites provides a suitable microenvironment where adaptive immune responses mainly occur. However, the microenvironment in the tumor draining lymph nodes (TDLNs) of patients with cancer appears to be in favor of tolerance. The effects of tumor cells on TDLNs have not been elaborated clearly. The present results have indicated that tumor cells may directly affect TDLNs by decreasing the fibroblastic reticular cell population that led to less interleukin‑7 secretion. As a result, the number of T cells in TDLNs declined with reduced survival signals. A decreased number of T cells in TDLNs means weakened ability of immune surveillance. Clinically, these results were also confirmed in LN biopsies from patients with colon cancer at different clinical stages. Results of the present study showed that tumor cells may directly inhibit the immunological function of TDLNs.

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1	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
2	Gao J, Zhao L, Wan YY and Zhu B: Mechanism of action of IL-7 and its potential applications and limitations in cancer immunotherapy. Int J Mol Sci. 16:10267–10280. 2015. View Article : Google Scholar : PubMed/NCBI
3	Lindau D, Gielen P, Kroesen M, Wesseling P and Adema GJ: The immunosuppressive tumour network: Myeloid-derived suppressor cells, regulatory T cells and natural killer T cells. Immunology. 138:105–115. 2013. View Article : Google Scholar : PubMed/NCBI
4	Malhotra D, Fletcher AL and Turley SJ: Stromal and hematopoietic cells in secondary lymphoid organs: Partners in immunity. Immunol Rev. 251:160–176. 2013. View Article : Google Scholar : PubMed/NCBI
5	Munn DH and Mellor AL: The tumor-draining lymph node as an immune-privileged site. Immunol Rev. 213:146–158. 2006. View Article : Google Scholar : PubMed/NCBI
6	Turley SJ, Fletcher AL and Elpek KG: The stromal and haematopoietic antigen-presenting cells that reside in secondary lymphoid organs. Nat Rev Immunol. 10:813–825. 2010. View Article : Google Scholar : PubMed/NCBI
7	Bajenoff M, Egen JG, Koo LY, Laugier JP, Brau F, Glaichenhaus N and Germain RN: Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity. 25:989–1001. 2006. View Article : Google Scholar : PubMed/NCBI
8	Zhao L, Gao J, Li Y, Liu L, Yang Y, Guo B and Zhu B: Disrupted homeostatic cytokines expression in secondary lymph organs during HIV infection. Int J Mol Sci. 17:4132016. View Article : Google Scholar : PubMed/NCBI
9	Zhao L, Chen J, Liu L, Gao J, Guo B and Zhu B: Essential role of TNF-alpha in development of spleen fibroblastic reticular cells. Cell Immunol. 293:130–136. 2015. View Article : Google Scholar : PubMed/NCBI
10	Link A, Vogt TK, Favre S, Britschgi MR, Acha-Orbea H, Hinz B, Cyster JG and Luther SA: Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat Immunol. 8:1255–1265. 2007. View Article : Google Scholar : PubMed/NCBI
11	Mueller SN and Germain RN: Stromal cell contributions to the homeostasis and functionality of the immune system. Nat Rev Immunol. 9:618–629. 2009.PubMed/NCBI
12	Onder L, Narang P, Scandella E, Chai Q, Iolyeva M, Hoorweg K, Halin C, Richie E, Kaye P, Westermann J, et al: IL-7-producing stromal cells are critical for lymph node remodeling. Blood. 120:4675–4683. 2012. View Article : Google Scholar : PubMed/NCBI
13	Fletcher AL, Malhotra D and Turley SJ: Lymph node stroma broaden the peripheral tolerance paradigm. Trends Immunol. 32:12–18. 2011. View Article : Google Scholar : PubMed/NCBI
14	Lee JW, Epardaud M, Sun J, Becker JE, Cheng AC, Yonekura AR, Heath JK and Turley SJ: Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. Nat Immunol. 8:181–190. 2007. View Article : Google Scholar : PubMed/NCBI
15	Dubrot J, Duraes FV, Potin L, Capotosti F, Brighouse D, Suter T, LeibundGut-Landmann S, Garbi N, Reith W, Swartz MA and Hugues S: Lymph node stromal cells acquire peptide-MHCII complexes from dendritic cells and induce antigen-specific CD4⁺ T cell tolerance. J Exp Med. 211:1153–1166. 2014. View Article : Google Scholar : PubMed/NCBI
16	Kittipatarin C and Khaled AR: Interlinking interleukin-7. Cytokine. 39:75–83. 2007. View Article : Google Scholar : PubMed/NCBI
17	Surh CD and Sprent J: Homeostasis of naive and memory T cells. Immunity. 29:848–862. 2008. View Article : Google Scholar : PubMed/NCBI
18	Rathmell JC, Farkash EA, Gao W and Thompson CB: IL-7 enhances the survival and maintains the size of naive T cells. J Immunol. 167:6869–6876. 2001. View Article : Google Scholar : PubMed/NCBI
19	Fry TJ and Mackall CL: The many faces of IL-7: From lymphopoiesis to peripheral T cell maintenance. J Immunol. 174:6571–6576. 2005. View Article : Google Scholar : PubMed/NCBI
20	Chappaz S and Finke D: The IL-7 signaling pathway regulates lymph node development independent of peripheral lymphocytes. J Immunol. 184:3562–3569. 2010. View Article : Google Scholar : PubMed/NCBI
21	Chappaz S, Gärtner C, Rodewald HR and Finke D: Kit ligand and Il7 differentially regulate Peyer's patch and lymph node development. J Immunol. 185:3514–3519. 2010. View Article : Google Scholar : PubMed/NCBI
22	Schmutz S, Bosco N, Chappaz S, Boyman O, Acha-Orbea H, Ceredig R, Rolink AG and Finke D: Cutting edge: IL-7 regulates the peripheral pool of adult ROR gamma+ lymphoid tissue inducer cells. J Immunol. 183:2217–2221. 2009. View Article : Google Scholar : PubMed/NCBI
23	Dukes CE: The surgical pathology of rectal cancer: President's address. Proc R Soc Med. 37:131–144. 1944.PubMed/NCBI
24	Fletcher AL, Malhotra D, Acton SE, Lukacs-Kornek V, Bellemare-Pelletier A, Curry M, Armant M and Turley SJ: Reproducible isolation of lymph node stromal cells reveals site-dependent differences in fibroblastic reticular cells. Front Immunol. 2:352011. View Article : Google Scholar : PubMed/NCBI
25	Sawa Y, Arima Y, Ogura H, Kitabayashi C, Jiang JJ, Fukushima T, Kamimura D, Hirano T and Murakami M: Hepatic interleukin-7 expression regulates T cell responses. Immunity. 30:447–457. 2009. View Article : Google Scholar : PubMed/NCBI
26	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
27	Zeng M, Paiardini M, Engram JC, Beilman GJ, Chipman JG, Schacker TW, Silvestri G and Haase AT: Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution. Blood. 120:1856–1867. 2012. View Article : Google Scholar : PubMed/NCBI
28	Zeng M, Smith AJ, Wietgrefe SW, Southern PJ, Schacker TW, Reilly CS, Estes JD, Burton GF, Silvestri G, Lifson JD, et al: Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections. J Clin Invest. 121:998–1008. 2011. View Article : Google Scholar : PubMed/NCBI
29	Astarita JL, Acton SE and Turley SJ: Podoplanin: Emerging functions in development, the immune system, and cancer. Front Immunol. 3:2832012. View Article : Google Scholar : PubMed/NCBI
30	de Aquino MT, Malhotra A, Mishra MK and Shanker A: Challenges and future perspectives of T cell immunotherapy in cancer. Immunol Lett. 166:117–133. 2015. View Article : Google Scholar : PubMed/NCBI
31	Gorelik L and Flavell RA: Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat Med. 7:1118–1122. 2001. View Article : Google Scholar : PubMed/NCBI
32	Wang Y, Han G, Wang K, Liu G, Wang R, Xiao H, Li X, Hou C, Shen B, Guo R, et al: Tumor-derived GM-CSF promotes inflammatory colon carcinogenesis via stimulating epithelial release of VEGF. Cancer Res. 74:716–726. 2014. View Article : Google Scholar : PubMed/NCBI
33	Mueller SN, Matloubian M, Clemens DM, Sharpe AH, Freeman GJ, Gangappa S, Larsen CP and Ahmed R: Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection. Proc Natl Acad Sci USA. 104:15430–15435. 2007. View Article : Google Scholar : PubMed/NCBI
34	Choi YK, Fallert BA, Murphey-Corb MA and Reinhart TA: Simian immunodeficiency virus dramatically alters expression of homeostatic chemokines and dendritic cell markers during infection in vivo. Blood. 101:1684–1691. 2003. View Article : Google Scholar : PubMed/NCBI
35	Zeng M, Haase AT and Schacker TW: Lymphoid tissue structure and HIV-1 infection: Life or death for T cells. Trends Immunol. 33:306–314. 2012. View Article : Google Scholar : PubMed/NCBI
36	Soudja SM, Henri S, Mello M, Chasson L, Mas A, Wehbe M, Auphan-Anezin N, Leserman L, Van den Eynde B and Schmitt-Verhulst AM: Disrupted lymph node and splenic stroma in mice with induced inflammatory melanomas is associated with impaired recruitment of T and dendritic cells. PloS One. 6:e226392011. View Article : Google Scholar : PubMed/NCBI
37	Imai K, Minamiya Y, Koyota S, Ito M, Saito H, Sato Y, Motoyama S, Sugiyama T and Ogawa J: Inhibition of dendritic cell migration by transforming growth factor-β1 increases tumor-draining lymph node metastasis. J Exp Clin Cancer Res. 31:32012. View Article : Google Scholar : PubMed/NCBI
38	Tang J, Nuccie BL, Ritterman I, Liesveld JL, Abboud CN and Ryan DH: TGF-beta down-regulates stromal IL-7 secretion and inhibits proliferation of human B cell precursors. J Immunol. 159:117–125. 1997.PubMed/NCBI