Immunotherapy for Precancerous Lesions of the Uterine Cervix

Abstract

The immunological milieu of premalignant lesions of the uterine cervix has not been sufficiently explored. The rationale for immunological approaches for the treatment of the premalignant lesions is as to prevent secondary premalignant lesions and their progression to cancer. Among the challenges of immunotherapeutic approaches for cancer are the multitudes of mechanisms by which cancers are known to subvert the immune defenses. Human papillomavirus (HPV) is known as a cause of uterine cervical cancer and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e., E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their molecular characteristics, these oncogenes represent a target for immunotherapy. The development of HPV-associated cancers depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage and immune evasion that enables the virus to go undetected for a long time. Noting that HPV-related lesions and tumors usually present MHC class I down-regulation, impaired antigen-processing ability, avoidance of T-cell mediated killing, increased immunosuppression due to Treg infiltration and secrete immunosuppressive cytokines. This chapter focuses on the immunological aspects of premalignant lesions of the uterine cervix and highlights strategies for immunotherapy and several promising immunotherapy technologies.