Dendritic Cells in Oral Cancer

Myeloid dendritic cells (DC) play a central regulatory role in the immune response to infections and cancer, and are normal residents of oral mucosa. During infections, DC undergo maturation and stimulate other immune system cells, but DC role and function in oral cancer is unclear. Objective: To evaluate the numbers and distribution of immature and mature dendritic cells (DC) in oral cancer. Materials and Methods: Cases analyzed include verrucous carcinoma (16 cases), carcinoma-in-situ (8), superficially-invasive squamous cell carcinoma (8), and chronic non-specific mucositis without pre-cancer or cancer (10). Adjacent sections of archival specimens (Surgical Oral Pathology Laboratory, College of Dentistry) were stained by standard immunohistochemistry using the alkaline phosphatase-Fast Red detection system for all resident myeloid DC (CD1a+) and mature DC (CD83+). Multiple sections and fields were examined under light microscopy for numbers (cell density per area) and location of labeled cells. Results: Several patterns of CD1a+ DC/CD83+ mature DC density were noted, which were grouped into four major categories: pattern #1 – high CD1a+/high CD83+; #2 - high CD1a+/low CD83+; #3 - low CD1a+/low CD83+; #4 - low CD1a+/high CD83+. We found pattern #1 in 7/10 chronic mucositis and 4/8 carcinoma-in-situ cases, but only 1/8 invasive SCC and 2/16 verrucous carcinoma cases, suggesting that DC influx and/or maturation may be impaired in SCC and verrucous carcinoma. Pattern #2 was dominant in invasive SCC (6/8 cases), while patterns #3 and #4 dominated verrucous carcinoma (8/16 and 7/16, respectively). Carcinoma-in-situ also showed pattern #3 (3/8) and #4 (1/8). Conclusion: These results suggest that immature DC influx and DC maturation may be negatively affected in oral cancer, the extent of which may depend on cancer subtype (verrucous vs. other) and stage (carcinoma-in-situ vs. superficially invasive SCC). Supported in part by American Cancer Society Grant #IN-122V, administered by The Holden Comprehensive Cancer Center.