期刊论文详细信息
Breast Cancer Research
Analysis of dendritic cells in tumor-free and tumor-containing sentinel lymph nodes from patients with breast cancer
Elizabeth A Grimm1  Kelly K Hunt2  Aysegul Sahin3  Nancy J Poindexter1 
[1] Department of Bioimmunotherapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
关键词: sentinel lymph node;    IL-12;    IL-10;    dendritic cells;    CD83;   
Others  :  1118739
DOI  :  10.1186/bcr808
 received in 2004-01-22, accepted in 2004-05-05,  发布年份 2004
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【 摘 要 】

Introduction

Sentinel lymph node (SLN) biopsy allows identification of the first lymph node into which a primary tumor drains. In breast cancer, identification of tumor cells in the SLNs is a predictor of the tumor's metastatic potential. In the present article, we tested the hypotheses that a positive immune response can occur in tumor-free SLNs and that the activation state of dendritic cells (DCs), the major antigen presenting cells within SLNs, predicts the immune status and metastatic potential of the tumor.

Methods

Fifty paraffin-embedded SLN sections, 25 tumor-free and 25 tumor-containing, from patients with breast cancer were analyzed by immunohistochemistry to determine the immune maturation state of their DCs. In addition, 12 lymph nodes from noncancer-containing breasts were analyzed. Tissues were stained with antibodies against CD3, MHC class II, CD1a, CD83, IL-10, and IL-12. Mature DCs were defined by CD83 expression and immature DCs by CD1a expression.

Results

We found a trend toward higher numbers of mature CD83-positive DCs in tumor-free SLNs than in tumor-containing SLNs (P = 0.07). In addition, tumor-free SLNs were more likely to contain cells expressing IL-10 (P = 0.02) and, to a lesser extent, IL-12 (P = 0.12). In contrast, when all SLNs, both tumor-free and tumor-containing, were compared with uninvolved lymph nodes, the numbers of mature and immature DCs were similar.

Conclusions

Our results suggest tumor-free SLNs are immunologically competent and potentially a site of tumor-specific T-cell activation, as evidenced by the presence of greater numbers of mature DCs and cytokine-producing cells in tumor-free SLNs.

【 授权许可】

   
2004 Poindexter et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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【 参考文献 】
  • [1]Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 1998, 392:245-252.
  • [2]Bell D, Chomarat P, Broyles D, Netto G, Harb GM, Lebecque S, Valladeau J, Davoust J, Palucka KA, Banchereau J: In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas. J Exp Med 1999, 190:1417-1425.
  • [3]Cella M, Sallusto F, Lanzavecchia A: Origin, maturation and antigen presenting function of dendritic cells. Curr Opin Immunol 1997, 9:10-16.
  • [4]Lapointe R, Toso JF, Butts C, Young HA, Hwu P: Human dendritic cells require multiple activation signals for the efficient generation of tumor antigen-specific T lymphocytes. Eur J Immunol 2000, 30:3291-3298.
  • [5]Giuliano AE, Jones RC, Brennan M, Statman R: Sentinel lymphadenectomy in breast cancer. J Clin Oncol 1997, 15:2345-2350.
  • [6]Leong SPL: Paradigm of metastasis for melanoma and breast cancer based on the sentinel lymph node experience. Ann Surg Oncol 2004, 11:192S-197S.
  • [7]Zhou LJ, Schwarting R, Smith HM, Tedder TF: A novel cell-surface molecule expressed by human interdigitating reticulum cells, Langerhans cells, and activated lymphocytes is a new member of the Ig superfamily. J Immunol 1992, 149:735-742.
  • [8]Zhou LJ, Tedder TF: CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. Proc Natl Acad Sci USA 1995, 93:2588-2592.
  • [9]Iwamota M, Shinohara H, Miyamoto A, Okuzawa M, Mabuchi H, Nohara H, Gon G, Toyoda M, Tanigawa N: Prognostic value of tumor-infiltrating dendritic cells expressing CD83 in human breast carcinomas. Int J Cancer 2003, 104:92-97.
  • [10]Kalinski P, Hilkens CMU, Wierenga EA, Kapsenberg ML: T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunol Today 1999, 20:561-567.
  • [11]Halak BK, Maguire HC, Lattime EC: Tumor-induced interleukin-10 inhibits type 1 immune responses directed at a tumor antigen as well as a non-tumor antigen present at the tumor site. Cancer Res 1999, 59:911-917.
  • [12]Jonuleit H, Schmitt E, Steinbrink K, Enk AH: Dendritic cells as a tool to induce anergic and regulatory T cells. Trends Immunol 2001, 22:394-400.
  • [13]Heufler C, Koch F, Stanzl U, Topar G, Wysocka M, Trinchieri G, Enk A, Steinman RM, Romani N, Schuler G: Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells. Eur J Immunol 1996, 26:659-668.
  • [14]Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G: Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J Exp Med 1996, 184:741-747.
  • [15]Huang RR, Wen D-R, Guo J, Giuliana AE, Nguyen M, Offodile R, Stern S, Turner R, Cochran AJ: Selective modulation of paracortical dendritic cells and T-lymphocytes in breast sentinel lymph nodes. Breast 2000, 6:225-232.
  • [16]Chu Y, Hu HM, Winter H, Wood WJ, Doran T, Lashley D, Bashey J, Schuster J, Wood J, Lowe BA, Vetto JT, Weinberg AD, Puri R, Smith JW, Urba WJ, Fox BA: Examining the immune response in sentinel lymph nodes of mice and men. Eur J Nucl Med 1999, 26(Suppl):S50-S53.
  • [17]Leong SPL, Peng M, Zhou Y-M, Vaquerano JE, Chang JWC: Cytokine profiles of sentinel lymph nodes draining the primary melanoma. Ann Surg Oncol 2002, 9:82-87.
  • [18]Vitale M, Rezzani R, Rodella L, Zauli G, Grigolato P, Cadei M, Hicklin DJ, Ferrone S: HLA class I antigen and transporter associated with antigen processing (TAP1 and TAP2) down-regulation in high-grade primary breast carcinoma lesions. Cancer Res 1998, 58:737-742.
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