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Erschienen in: Annals of Surgical Oncology 5/2017

28.11.2016 | Urologic Oncology

Tumor Infiltrating Mast Cells (TIMs) Confers a Marked Survival Advantage in Nonmetastatic Clear-Cell Renal Cell Carcinoma

verfasst von: Hangcheng Fu, MD, Yu Zhu, MD, Yiwei Wang, MD, Zheng Liu, MD, Junyu Zhang, MD, Zewei Wang, MD, Huyang Xie, MD, Bo Dai, MD, Jiejie Xu, MD, PhD, Dingwei Ye, MD

Erschienen in: Annals of Surgical Oncology | Ausgabe 5/2017

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Abstract

Purpose

The role played by the innate immune system in determining the clinical outcome of clear-cell renal cell carcinoma (ccRCC) was still blurred. This study was designed to investigate the prognostic significance of tumor infiltrating mast cells (TIMs) in ccRCC.

Methods

The study retrospectively enrolled a training set (474 patients) and a validation set (188 patients) with nonmetastasis (pT1-4N0M0) ccRCC from two institutional medical centers of China. TIMs was evaluated by immunohistochemical staining of tryptase and its association with clinicopathologic features and prognosis were evaluated.

Results

In ccRCC tissues, TIMs ranged from 0 to 103 cells/mm2 and 0 to 113 cells/mm2 in the training set and validation set, respectively. TIMs was negatively correlated with tumor size (P < 0.001 and P < 0.001, respectively), pathological T stage (P = 0.005 and P = 0.007, respectively) and Fuhrman grade (P < 0.001 and P < 0.001, respectively). Patients with abundant TIMs infiltration showed significantly longer cancer-specific survival in the training cohort and the validation cohort (P < 0.001 and P < 0.001). Patients with abundant mast cell infiltration showed significantly longer overall survival in the TCGA cohort (P < 0.001). Moreover, multivariate analysis identified TIMs as an independent prognostic factor for cancer-specific survival (CSS) and relapse-free survival (RFS). Also, TIMs was significantly correlated with CSS and RFS of the mediate and high-risk patients in the training cohort and the validation cohort.

Conclusions

TIMs density is a powerful independent prognostic factor for CSS and RFS in patients with nonmetastasis (pT1-4N0M0) ccRCC.
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Literatur
1.
2.
Zurück zum Zitat Ljungberg B, Bensalah K, Canfield S, et al. EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol. 2015;67(5):913–24.CrossRefPubMed Ljungberg B, Bensalah K, Canfield S, et al. EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol. 2015;67(5):913–24.CrossRefPubMed
3.
Zurück zum Zitat Motzer RJ, Agarwal N, Beard C, et al. NCCN clinical practice guidelines in oncology: kidney cancer. J Natl Compr Cancer Netw JNCCN. 2009;7(6):618–30. Motzer RJ, Agarwal N, Beard C, et al. NCCN clinical practice guidelines in oncology: kidney cancer. J Natl Compr Cancer Netw JNCCN. 2009;7(6):618–30.
4.
Zurück zum Zitat Inman BA, Harrison MR, George DJ. Novel immunotherapeutic strategies in development for renal cell carcinoma. Eur Urol. 2013;63(5):881–9.CrossRefPubMed Inman BA, Harrison MR, George DJ. Novel immunotherapeutic strategies in development for renal cell carcinoma. Eur Urol. 2013;63(5):881–9.CrossRefPubMed
5.
Zurück zum Zitat Rosenberg SA, Lotze MT, Yang JC, et al. Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst. 1993;85(8):622–32.CrossRefPubMed Rosenberg SA, Lotze MT, Yang JC, et al. Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst. 1993;85(8):622–32.CrossRefPubMed
6.
Zurück zum Zitat Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–13.CrossRefPubMed Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–13.CrossRefPubMed
7.
Zurück zum Zitat Dimitriadou V, Koutsilieris M. Mast cell-tumor cell interactions: for or against tumour growth and metastasis? Anticancer Res. 1997;17(3A):1541–9.PubMed Dimitriadou V, Koutsilieris M. Mast cell-tumor cell interactions: for or against tumour growth and metastasis? Anticancer Res. 1997;17(3A):1541–9.PubMed
8.
Zurück zum Zitat Beer TW, Ng LB, Murray K. Mast cells have prognostic value in Merkel cell carcinoma. Am J Dermatopathol. 2008;30(1):27–30.CrossRefPubMed Beer TW, Ng LB, Murray K. Mast cells have prognostic value in Merkel cell carcinoma. Am J Dermatopathol. 2008;30(1):27–30.CrossRefPubMed
9.
Zurück zum Zitat Giusca SE, Caruntu ID, Cimpean AM, et al. Tryptase-positive and CD117 positive mast cells correlate with survival in patients with liver metastasis. Anticancer Res. 2015;35(10):5325–31.PubMed Giusca SE, Caruntu ID, Cimpean AM, et al. Tryptase-positive and CD117 positive mast cells correlate with survival in patients with liver metastasis. Anticancer Res. 2015;35(10):5325–31.PubMed
10.
Zurück zum Zitat Ju MJ, Qiu SJ, Gao Q, et al. Combination of peritumoral mast cells and T-regulatory cells predicts prognosis of hepatocellular carcinoma. Cancer Sci. 2009;100(7):1267–74.CrossRefPubMed Ju MJ, Qiu SJ, Gao Q, et al. Combination of peritumoral mast cells and T-regulatory cells predicts prognosis of hepatocellular carcinoma. Cancer Sci. 2009;100(7):1267–74.CrossRefPubMed
11.
Zurück zum Zitat Nonomura N, Takayama H, Nishimura K, et al. Decreased number of mast cells infiltrating into needle biopsy specimens leads to a better prognosis of prostate cancer. Br J Cancer. 2007;97(7):952–6.PubMedPubMedCentral Nonomura N, Takayama H, Nishimura K, et al. Decreased number of mast cells infiltrating into needle biopsy specimens leads to a better prognosis of prostate cancer. Br J Cancer. 2007;97(7):952–6.PubMedPubMedCentral
12.
Zurück zum Zitat Ogino S, Shima K, Baba Y, et al. Colorectal cancer expression of peroxisome proliferator-activated receptor gamma (PPARG, PPARgamma) is associated with good prognosis. Gastroenterology. 2009;136(4):1242–50.CrossRefPubMed Ogino S, Shima K, Baba Y, et al. Colorectal cancer expression of peroxisome proliferator-activated receptor gamma (PPARG, PPARgamma) is associated with good prognosis. Gastroenterology. 2009;136(4):1242–50.CrossRefPubMed
13.
Zurück zum Zitat Strouch MJ, Cheon EC, Salabat MR, et al. Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. Clin Cancer Res. 2010;16(8):2257–65.CrossRefPubMedPubMedCentral Strouch MJ, Cheon EC, Salabat MR, et al. Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. Clin Cancer Res. 2010;16(8):2257–65.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Welsh TJ, Green RH, Richardson D, Waller DA, O’Byrne KJ, Bradding P. Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J Clin Oncol. 2005;23(35):8959–67.CrossRefPubMed Welsh TJ, Green RH, Richardson D, Waller DA, O’Byrne KJ, Bradding P. Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J Clin Oncol. 2005;23(35):8959–67.CrossRefPubMed
15.
Zurück zum Zitat Taskinen M, Karjalainen-Lindsberg ML, Leppa S. Prognostic influence of tumor-infiltrating mast cells in patients with follicular lymphoma treated with rituximab and CHOP. Blood. 2008;111(9):4664–7.CrossRefPubMed Taskinen M, Karjalainen-Lindsberg ML, Leppa S. Prognostic influence of tumor-infiltrating mast cells in patients with follicular lymphoma treated with rituximab and CHOP. Blood. 2008;111(9):4664–7.CrossRefPubMed
16.
Zurück zum Zitat Boesiger J, Tsai M, Maurer M, et al. Mast cells can secrete vascular permeability factor/vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of fc epsilon receptor I expression. J Exp Med. 1998;188(6):1135–45.CrossRefPubMedPubMedCentral Boesiger J, Tsai M, Maurer M, et al. Mast cells can secrete vascular permeability factor/vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of fc epsilon receptor I expression. J Exp Med. 1998;188(6):1135–45.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Hershko AY, Suzuki R, Charles N, et al. Mast cell interleukin-2 production contributes to suppression of chronic allergic dermatitis. Immunity. 2011;35(4):562–71.CrossRefPubMedPubMedCentral Hershko AY, Suzuki R, Charles N, et al. Mast cell interleukin-2 production contributes to suppression of chronic allergic dermatitis. Immunity. 2011;35(4):562–71.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Guldur ME, Kocarslan S, Ozardali HI, Ciftci H, Dincoglu D, Gumus K. The relationship of mast cells and angiogenesis with prognosis in renal cell carcinoma. JPMA. 2014;64(3):300–3. Guldur ME, Kocarslan S, Ozardali HI, Ciftci H, Dincoglu D, Gumus K. The relationship of mast cells and angiogenesis with prognosis in renal cell carcinoma. JPMA. 2014;64(3):300–3.
20.
Zurück zum Zitat Tuna B, Yorukoglu K, Unlu M, Mungan MU, Kirkali Z. Association of mast cells with microvessel density in renal cell carcinomas. Eur Urol. 2006;50(3):530–4.CrossRefPubMed Tuna B, Yorukoglu K, Unlu M, Mungan MU, Kirkali Z. Association of mast cells with microvessel density in renal cell carcinomas. Eur Urol. 2006;50(3):530–4.CrossRefPubMed
21.
Zurück zum Zitat Zisman A, Pantuck AJ, Wieder J, et al. Risk group assessment and clinical outcome algorithm to predict the natural history of patients with surgically resected renal cell carcinoma. J Clin Oncol. 2002;20(23):4559–66.CrossRefPubMed Zisman A, Pantuck AJ, Wieder J, et al. Risk group assessment and clinical outcome algorithm to predict the natural history of patients with surgically resected renal cell carcinoma. J Clin Oncol. 2002;20(23):4559–66.CrossRefPubMed
22.
Zurück zum Zitat Fu H, Liu Y, Xu L, et al. Galectin-9 predicts postoperative recurrence and survival of patients with clear-cell renal cell carcinoma. Tumour Biol. 2015;36(8):5791–9.CrossRefPubMed Fu H, Liu Y, Xu L, et al. Galectin-9 predicts postoperative recurrence and survival of patients with clear-cell renal cell carcinoma. Tumour Biol. 2015;36(8):5791–9.CrossRefPubMed
23.
24.
Zurück zum Zitat Blair RJ, Meng H, Marchese MJ, et al. Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor. J Clin Investig. 1997;99(11):2691–700.CrossRefPubMedPubMedCentral Blair RJ, Meng H, Marchese MJ, et al. Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor. J Clin Investig. 1997;99(11):2691–700.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Saleem SJ, Martin RK, Morales JK, et al. Cutting edge: mast cells critically augment myeloid-derived suppressor cell activity. J Immunol. 2012;189(2):511–5.CrossRefPubMedPubMedCentral Saleem SJ, Martin RK, Morales JK, et al. Cutting edge: mast cells critically augment myeloid-derived suppressor cell activity. J Immunol. 2012;189(2):511–5.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Ribatti D. Mast cells and macrophages exert beneficial and detrimental effects on tumor progression and angiogenesis. Immunol Lett. 2013;152(2):83–8.CrossRefPubMed Ribatti D. Mast cells and macrophages exert beneficial and detrimental effects on tumor progression and angiogenesis. Immunol Lett. 2013;152(2):83–8.CrossRefPubMed
27.
Zurück zum Zitat Ozdemir O. Flow cytometric mast cell-mediated cytotoxicity assay: a three-color flow cytometric approach using monoclonal antibody staining with annexin V/propidium iodide co-labeling to assess human mast cell-mediated cytotoxicity by fluorosphere-adjusted counts. J Immunol Methods. 2011;365(1–2):166–73.CrossRefPubMed Ozdemir O. Flow cytometric mast cell-mediated cytotoxicity assay: a three-color flow cytometric approach using monoclonal antibody staining with annexin V/propidium iodide co-labeling to assess human mast cell-mediated cytotoxicity by fluorosphere-adjusted counts. J Immunol Methods. 2011;365(1–2):166–73.CrossRefPubMed
28.
Zurück zum Zitat Huang B, Lei Z, Zhang GM, et al. SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment. Blood. 2008;112(4):1269–79.CrossRefPubMedPubMedCentral Huang B, Lei Z, Zhang GM, et al. SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment. Blood. 2008;112(4):1269–79.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Ribatti D, Crivellato E. Mast cells, angiogenesis and cancer. Adv Exp Med Biol. 2011;716:270–88.CrossRefPubMed Ribatti D, Crivellato E. Mast cells, angiogenesis and cancer. Adv Exp Med Biol. 2011;716:270–88.CrossRefPubMed
30.
Zurück zum Zitat Buonerba C, Di Lorenzo G, Sonpavde G. Combination therapy for metastatic renal cell carcinoma. Ann Transl Med. 2016;4(5):100.CrossRef Buonerba C, Di Lorenzo G, Sonpavde G. Combination therapy for metastatic renal cell carcinoma. Ann Transl Med. 2016;4(5):100.CrossRef
31.
Zurück zum Zitat Ravaud A, Motzer RJ, Pandha HS, et al. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med. Oct 9 2016. Ravaud A, Motzer RJ, Pandha HS, et al. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med. Oct 9 2016.
32.
Zurück zum Zitat Fleischmann A, Schlomm T, Kollermann J, et al. Immunological microenvironment in prostate cancer: high mast cell densities are associated with favorable tumor characteristics and good prognosis. Prostate. 2009;69(9):976-81.CrossRefPubMed Fleischmann A, Schlomm T, Kollermann J, et al. Immunological microenvironment in prostate cancer: high mast cell densities are associated with favorable tumor characteristics and good prognosis. Prostate. 2009;69(9):976-81.CrossRefPubMed
Metadaten
Titel
Tumor Infiltrating Mast Cells (TIMs) Confers a Marked Survival Advantage in Nonmetastatic Clear-Cell Renal Cell Carcinoma
verfasst von
Hangcheng Fu, MD
Yu Zhu, MD
Yiwei Wang, MD
Zheng Liu, MD
Junyu Zhang, MD
Zewei Wang, MD
Huyang Xie, MD
Bo Dai, MD
Jiejie Xu, MD, PhD
Dingwei Ye, MD
Publikationsdatum
28.11.2016
Verlag
Springer International Publishing
Erschienen in
Annals of Surgical Oncology / Ausgabe 5/2017
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5702-5

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