Infiltration of dendritic cells and NK cells into the sentinel lymph node in oral cavity cancer☆
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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2023, Biochemical PharmacologyTiming of sentinel node biopsy independently predicts disease-free and overall survival in clinical stage I-II melanoma patients: A multicentre study of the Italian Melanoma Intergroup (IMI)
2020, European Journal of CancerCitation Excerpt :The SN is the first lymphoid organ that tumour antigens meet after being released from a primary tumour into the lymphatic drainage. SNs are thought to be more closely associated with antitumour immunity than non-SNs [22]. However, the presence of melanoma inhibits an immune response by releasing immunosuppressive cytokines and creating an immunosuppressive microenvironment [23,24].
Primary tumor induces sentinel lymph node lymphangiogenesis in oral squamous cell carcinoma
2010, Oral OncologyCitation Excerpt :Similarly, Angeli et al. have described that lymph node lymphangiogenesis appears to promote the migration of dendritic cells (DCs) toward the draining lymph node in inflamed lymph nodes.20 Indeed, our previous study indicated that S-100 and CD1a+ immature DCs infiltrated significantly into tumor-free SLNs compared to non-SLNs in OSCC.21 CD11b+ macrophages22 and certain DCs, including monocyte-derived immature DCs,23 airway DCs,24 and corneal DCs25, have been reported to express VEGFR-3; therefore, active lymphangiogenesis within SLNs induced by VEGF-C may concomitantly lead to increased migration of APCs, such as macrophages and DCs.
CPA6, FMO2, LGI1, SIAT1 and TNC are differentially expressed in early- and late-stage oral squamous cell carcinoma - A pilot study
2008, Oral OncologyCitation Excerpt :The fact that LGI1 is downregulated in healthy oral mucosa of patients with advanced oral cancer suggests that lack of LGI1 expression in oral mucosa may result in reduced ability to suppress oral cancer development and progression and that high expression levels may help to prevent tumour propagation. From this gene expression pattern it could be hypothesised that LGI1 might be involved in local anti-tumour defence systems as they have been described also for immunologic defence through antigen presenting dendritic cells.52,53 A predominantly biometrical approach was used for the identification of genes which may be involved in the progression of oral cancer.
Head and Neck Squamous Cell Carcinoma: Sentinel Node or Selective Neck Dissection
2007, Surgical Oncology Clinics of North AmericaCitation Excerpt :One study showed that S-100+ and CD1a+ dendritic cells infiltrated significantly into SLNs compared with non-SLNs. These and similar results suggested that more significant immune responses against cancer occur in SLNs than in non-SLNs [98]. All these efforts may help experts understand the process of metastasis.
Immunobiology of the sentinel lymph node and its potential role for antitumour immunity
2006, Lancet OncologyCitation Excerpt :Nevertheless, these effects of immunosuppression on dendritic cells within SLNs in patients with non-small-cell lung cancer seem to be similar to other cases of malignant tumours such as melanoma and breast cancer. In oral cancer, an increase in S-100+, CD1a+ and other markers expressed by dendritic cells has been reported in tumour-free SLNs compared with non-SLNs.42 However, only S-100+ dendritic cells had a greater concentration in tumour-infiltrated SLNs than in non-SLNs.
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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).