Elsevier

Oral Oncology

Volume 41, Issue 1, January 2005, Pages 89-96
Oral Oncology

Infiltration of dendritic cells and NK cells into the sentinel lymph node in oral cavity cancer

https://doi.org/10.1016/j.oraloncology.2004.07.004Get rights and content

Summary

The sentinel lymph node (SLN) is regarded as the first tumor-draining lymph node, which may be the initial site activated by tumor antigens. To clarify the immunological functions of SLNs, a total of 89 tumor-free regional lymph nodes (41 SLNs and 48 non-SLNs) were obtained from 12 patients with oral cavity cancer, and infiltration of both DCs and NK cells was determined by immunohistochemistry. S-100+ and CD1a+ DCs infiltrated significantly into SLNs compared to non-SLNs. Analysis in each of the pN0 and pN+ patients showed that all the DC markers in pN0 patients and only S-100+ in pN+ patients were significantly more abundant in SLNs. Moreover, infiltration of CD83+ DCs was less in pN+ patients than in pN0 patients. These results suggest that more significant immune responses against cancer occur in SLNs than in non-SLNs. However the progression of disease including nodal disease may cause systemic immunosuppression.

Introduction

The sentinel lymph node (SLN) concept has been introduced in head and neck cancer to evaluate neck metastases more precisely following its successful application in melanoma1 and breast cancer.2 The concept is that the pathologic evaluation of the SLN reflects the stage of regional nodal status, so patients eligible for neck treatment can be selected more accurately. Since SLNs is the first draining lymph nodes from the primary tumor, SLNs would be in first contact with tumor antigens released from a primary tumor through lymphatic drainage. Therefore, the SLNs may be the initial sites activated by tumor antigens, where a specific immune response leading to tumor rejection can be induced.

The key to the immune response against tumor antigens, is a highly specialized antigen-presenting cells (APCs). Dendritic cells (DCs) express not only a high level of major histocompatibility complex (MHC) molecules, but also a high level of adhesion and co-stimulatory molecules, which are critical for activating naïve T cells. Accordingly, DCs are the most potent APCs and the only APCs capable of inducing cytotoxic T lymphocytes (CTLs) from naı¨ve T cells. Thus, DCs play a central role in the regulation and maintenance of a cellular immune response against cancer. In fact, the DCs’s role is supported by several studies that show that DCs density at a primary site is positively associated with better prognosis for various types of cancer, including lung3, colon4, 5, 6, and head and neck.7, 8 In addition, Tsujitani et al. demonstrated that DCs in the regional lymph nodes (RLNs) may be also important for establishing effective immunologic defense against cancer.9 Among RLNs, SLNs may be more closely associated with antitumor immunity, as the first draining lymph node from the site of a primary tumor, when compared to non-SLNs. In this study, we performed an immunohistochemical study to investigate whether the infiltration of immune cells including DCs, T cells and NK cells, differs in SLNs vs non-SLNs in patients with oral cavity cancer.

Section snippets

Patients and SLN identification

The SLNs were obtained from 12 patients with oral cavity cancer, who enrolled in a clinical trial of sentinel node biopsy performed at Gunma University Hospital, which was approved by the Institutional Review Board (Table 1). All patients signed an informed consent form before entry on the protocol. The detailed method for detection of SLN has been described previously.10 Briefly, the day before surgery, 2 ml of [99mTc] colloidal rhenium sulphide (NACOCIS, CIS bio international, France) was

SLN identification

Twelve patients with oral squamous cell carcinoma (OSCC) were enrolled in this study. The patients had no anticancer drug or radiation therapy before surgery. In all 12 patients, the SLNs were successfully identified and 51 SLNs were found in total. The mean number of SLNs per case was 4.3, which ranged from 2 to 7 nodes. All lymph node specimens, including SLNs, were examined histopathologically, and seven were classified pathologically as pN0 while five were pN+. Forty-two of 51 SLNs did not

Discussion

Immune responses against cancer initially occur in lymph nodes, where tumor cells may be recognized by immune cells, such as NK cells, APCs, CD8+ CTLs, and CD4+ T helper cells. Therefore, the RLNs play a crucial role in the interaction between a developing tumor and establishment of the host immune defense, sustaining the initiation and possibly the maintenance of tumor immunity. Recently, a new diagnostic technique has become available enabling detection of first tumor-draining lymph nodes,

Acknowledgement

We thank Dr. Theresa L. Whiteside for critical reading and comments, and Ms. Masako Saito for technical cooperation.

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    This work was supported in part by Ministry of Education, Science, Sports and Culture, Japan (Grants-in-Aid of Scientific Research and Priority Areas).

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