HLA-restricted cytotoxic T-lymphocyte (CTL) recognition of human papillomavirus (HPV) oncogene products may be important in the control of the HPV infections associated with the development of cervical cancer. We have identified, in HLA-B7 individuals, a consistent variation in the HPV16 E6 oncoprotein sequence, which alters an HLA-B7 peptide binding epitope in a way likely to influence immune recognition by CTLs. These results illustrate a biologically relevant mechanism for escape from immune surveillance of HPV16 in HLA-B7 individuals. Thus, both HLA type and HPV16 strain variation need to be considered in the screening of at-risk individuals and for the rational design of anti-HPV vaccines.
Immune recognition and elimination of tumors protects us from cancer. Tumors frequently manifest immunosuppressive mechanisms to avoid anti-tumor immunity and thereby become clinical challenges. The immune system is quite sensitive to microbial pathogens and microbes or microbial extracts are very effective adjuvants to stimulate an immune response. Here we present the results of treatment of established cutaneous B16F10 murine melanoma by intratumoral injection of a fully attenuated uracil auxotroph strain of Toxoplasma gondii (ΔCPS) that cannot replicate in vivo. ΔCPS exposure breaks immunosuppression and stimulates a strong Th1 antitumor immune response in vivo that cures established primary melanoma and develops immune memory that confers protection against subsequent rechallenges. This treatment modifies the tumor microenvironment, increases MHC Class I expression on tumor cells and reverses immunosuppression, permitting a tumor-antigen specific CD8 T cell response to eliminate the tumor. The approach has efficacy against multiple tumor types and has potential for clinical utility.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.