Mission impossible: How HPV-associated head and neck cancers escape a primed immune response

摘要

Human papillomavirus (HPV) is recognized as the causative agent in a growing subset of head and neck cancers. HPV-associ-ated head and neck squamous cell carcinomas (HPV-HNSCC) arise within the lymphoid tissue of the palatine and lingual tonsils, and are distinguished from their tobacco-related, non-HPV counterparts by a characteristic infiltration of lymphocytes within the stroma and tumor nests. Yet, despite this immune-rich milieu in which they arise, HPV-HNSCCs are able to evade immune recognition and survive. It is this paradox of how these tumors develop and thrive in the microenvironment of trafficking lymphocytes that we set forth to elucidate.The improbability of the mission accomplished by HPV-HNSCC in escaping immune recognition is highlighted by two important points. First, HPV infects a lymphoid organ (the palatine and lingual tonsils) and yet escapes immune recognition and clearance as it transforms virally infected cells into cancer. Second, all HPV-infected cells express unique viral proteins, such as the E6 and E7 antigens, which are foreign and highly immunogenic to the host and, thus, immune responses against virus-infected cells should be strongly activated and not tolerant. The existing harmony between tumor cells and surrounding immune cells in HPV-HNSCC provides a unique opportunity to unveil novel mechanisms of tumor immune escape which may be applicable to multiple tumor types.