Presence and Distribution of Plasmacytoid Dendritic Cells in Head and Neck Lymphoepithelial Carcinoma. Possible Role in the Pathogenesis and Potential Therapeutic Target
Ana Maria Cano-Valdez, Clotilde Guajardo-Lopez, Karina Ordonez-Pantoja, Esther Gonzalez-Conde, Ana Graciela Puebla-Mora, Alejandro Mohar-Betancourt. Instituto Nacional de Cancerologia, Mexico City, Mexico; Centro Oncologico Tamaulipas, Ciudad Victoria, Mexico; Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico
Background: Plasmacytoid dendritic cells (PDCs) are essential part of the immune system through the production of interferon-alpha (IFNα) and antigen presentation. They can be activated by stimulation of "toll-like" receptors (TLRs). The TLR-9 stimulation induces production of IFNα, chemokines and cytokines that promote recruitment of NK cells, activated T lymphocytes and macrophages. It has been suggested that in tumors of viral etiology some components of microorganism interact with elements of tumoral microenvironment and induce TLRs dysfunction. Thus, the limited response of PDCs contributes to reduction of the immune response during chronic viral infections and oncogenesis. The role of PDCs in lymphoepithelial carcinoma (LEC) has not been studied previously.
Design: We reviewed the Surgical Pathology archives of the National Cancer Institute to identify and select those cases diagnosed as H&N LEC. A control group (non-neoplastic lymphoid tissue) was also selected for comparison. Tissue microarrays and immunohistochemistry for CD123, CD4, CD56 TLR-9 and LMP-1, plus in situ hybridization (EBER) were performed. Clinical records were reviewed and data were analyzed through descriptive statistics.
Results: 32 patients with LEC, 22 men and 10 women with a mean age of 49.9 yrs were included. In LEC group, PDCs were identified primarily in the transition between the tumor nests and lymphoid cells. In the control cases, PDCs where found in the interfollicular space and around post-capillary venules. TLR-9 expression by PDCs was observed only in 3 cases of LEC. EBV infection was confirmed by EBER in 18 cases.
Conclusions: This is the first study exploring the role of PDCs in the pathogenesis of LEC. It was observed decreased expression of TLR-9, suggesting dysfunction of these receptors. This limited response of PDCs could contribute to reduce antimicrobial and antitumor immune response, participating in oncogenesis. Therefore, they represent a potential target for new therapeutic strategies based on TLR agonists. At present, drugs with this function have been developed. CpG oligodeoxynucleotides (ODNs) have been tested with promising results as adjuvants in combination with other agents in some tumors. Our results suggest that TLR agonists could be used as adjunctive target therapy in the management of LEC.
Category: Head & Neck
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 209, Wednesday Morning