Interleukin-17-producing cell infiltration in the breast cancer tumour microenvironment is a poor prognostic factor

被引:126
作者
Chen, Wen-Chung [1 ]
Lai, Yu-Hsuan [2 ]
Chen, Hung-Yu [2 ]
Guo, How-Ran [3 ]
Su, Ih-Jen [4 ]
Chen, Helen H. W. [2 ]
机构
[1] Natl Cheng Kung Univ, Coll Med, Natl Cheng Kung Univ Hosp, Dept Pathol, Tainan 704, Taiwan
[2] Natl Cheng Kung Univ, Coll Med, Natl Cheng Kung Univ Hosp, Dept Radiat Oncol, Tainan 704, Taiwan
[3] Natl Cheng Kung Univ, Coll Med, Natl Cheng Kung Univ Hosp, Dept Environm & Occupat Hlth, Tainan 704, Taiwan
[4] Natl Hlth Res Inst, Natl Inst Infect Dis & Vaccinol, Tainan, Taiwan
关键词
breast cancer; inflammation; interleukin-17; prognosis; tumour microenvironment; REGULATORY T-CELLS; HUMAN T(H)17 CELLS; TH17; CELLS; HELPER-CELLS; TGF-BETA; GROWTH; IMMUNITY; IL-17; DIFFERENTIATION; GAMMA;
D O I
10.1111/his.12156
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
AimsInterleukin-17 (IL-17) is a proinflammatory cytokine that is most prominently produced by T-helper type 17 (Th17) cells, a distinct CD4+ T-helper cell subset. The aim of this study was to investigate the level of IL-17-producing cells in the breast cancer tumour microenvironment and its prognostic role. Methods and resultsA total of 207 breast carcinoma specimens were assessed by IL-17 immunohistochemistry, and the findings were correlated with clinicopathological parameters. We found that increased numbers of IL-17-producing cells were correlated with high histological grade, negative ER/PR status, and triple-negative molecular subtypes segregated by immunoprofiles. However, they did not correlate with stage, tumour size, nodal status, HER2 status, or histological type. Patients with tumours with high numbers of IL-17-producing cells had shorter disease-free survival (DFS) than patients with tumours with low numbers of IL-17-producing cells (P<0.01). In multivariate analysis, high IL-17 level [hazard ratio (HR) 2.24; 95% CI 1.06-4.75], advanced T stage (HR 2.73; 95% CI 1.30-5.73), positive HER2 status (HR 4.88; 95% CI 1.47-16.18) and triple-negative subtype (HR 7.46; 95% CI 1.38-40.36) were significant prognostic factors for DFS. ConclusionsOur results indicate that a high level of IL-17-producing cells in the breast cancer tumour microenvironment is a poor prognostic factor.
引用
收藏
页码:225 / 233
页数:9
相关论文
共 42 条
[1]   Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells [J].
Acosta-Rodriguez, Eva V. ;
Napolitani, Giorgio ;
Lanzavecchia, Antonio ;
Sallusto, Federica .
NATURE IMMUNOLOGY, 2007, 8 (09) :942-949
[2]   Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse [J].
Bates, Gaynor J. ;
Fox, Stephen B. ;
Han, Cheng ;
Leek, Russell D. ;
Garcia, Jose F. ;
Harris, Adrian L. ;
Banham, Alison H. .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (34) :5373-5380
[3]   Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism [J].
Benchetrit, F ;
Ciree, A ;
Vives, V ;
Warnier, G ;
Gey, A ;
Sautès-Fridman, C ;
Fossiez, F ;
Haicheur, N ;
Fridman, WH ;
Tartour, E .
BLOOD, 2002, 99 (06) :2114-2121
[4]   Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J].
Bettelli, E ;
Carrier, YJ ;
Gao, WD ;
Korn, T ;
Strom, TB ;
Oukka, M ;
Weiner, HL ;
Kuchroo, VK .
NATURE, 2006, 441 (7090) :235-238
[5]   TH-17 cells in the circle of immunity and autoimmunity [J].
Bettelli, Estelle ;
Oukka, Mohamed ;
Kuchroo, Vijay K. .
NATURE IMMUNOLOGY, 2007, 8 (04) :345-350
[6]   Cancer immunotherapy: A treatment for the masses [J].
Blattman, JN ;
Greenberg, PD .
SCIENCE, 2004, 305 (5681) :200-205
[7]   Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells [J].
Chen, Zhi ;
Laurence, Arian ;
Kanno, Yuka ;
Pacher-Zavisin, Margit ;
Zhu, Bing-Mei ;
Tato, Cristina ;
Yoshimura, Akihiko ;
Hennighausen, Lothar ;
O'Shea, John J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (21) :8137-8142
[8]   Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor [J].
Cosmi, Lorenzo ;
De Palma, Raffaele ;
Santarlasci, Veronica ;
Maggi, Laura ;
Capone, Manuela ;
Frosali, Francesca ;
Rodolico, Gabriella ;
Querci, Valentina ;
Abbate, Gianfranco ;
Angeli, Roberta ;
Berrino, Liberato ;
Fambrini, Massimiliano ;
Caproni, Marzia ;
Tonelli, Francesco ;
Lazzeri, Elena ;
Parronchi, Paola ;
Liotta, Francesco ;
Maggi, Enrico ;
Romagnani, Sergio ;
Annunziato, Francesco .
JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (08) :1903-1916
[9]   Interferons, immunity and cancer immunoediting [J].
Dunn, Gavin P. ;
Koebel, Catherine M. ;
Schreiber, Robert D. .
NATURE REVIEWS IMMUNOLOGY, 2006, 6 (11) :836-848
[10]   Future perspectives: should Th17 cells be considered as a possible therapeutic target in acute myeloid leukemia patients receiving allogeneic stem cell transplantation? [J].
Ersvaer, Elisabeth ;
Melve, Guro Kristin ;
Bruserud, Oystein .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2011, 60 (12) :1669-1681