Analysis of dendritic cells in tumor-free and tumor-containing sentinel lymph nodes from patients with breast cancer.

Nancy J Poindexter,Kelly K Hunt,Elizabeth A Grimm,Aysegul Sahin

doi:10.1186/bcr808

Nancy J Poindexter, Kelly K Hunt + Show 2 more

Open Access

https://doi.org/10.1186/bcr808

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Abstract

IntroductionSentinel 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.MethodsFifty 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.ResultsWe 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.ConclusionsOur 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.

Highlights

Sentinel lymph node (SLN) biopsy allows identification of the first lymph node into which a primary tumor drains
We found a trend toward higher numbers of mature CD83-positive dendritic cells (DCs) in tumor-free sentinel lymph node (SLN) than in tumor-containing SLNs (P = 0.07)
When tumors were sorted by nuclear grade and SLN status, we found that the number of CD1apositive, immunologically immature DCs was significantly greater (P = 0.01) in the tumor-containing SLNs draining from grade III tumors than in the tumor-free SLNs draining from grade III tumors (Table 2)

Summary

Introduction

Sentinel lymph node (SLN) biopsy allows identification of the first lymph node into which a primary tumor drains. After receiving the correct cytokine signals, the mature, peptide-loaded DCs migrate from the tumor to the first draining lymph node, referred to as the sentinel lymph node (SLN). In the SLN, naïve T cells are activated by the peptide-loaded mature DCs. In the SLN, naïve T cells are activated by the peptide-loaded mature DCs These T cells undergo clonal expansion, gain effector function, and circulate back to the tumor, where their function is to lyse tumor cells. Evidence to support this process comes almost entirely from in vitro experiments [1,2,3,4]

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