@article {1434679,
	title = {Anti-tumor immunity induced by ectopic expression of viral antigens is transient and limited by immune escape},
	journal = {Oncoimmunology},
	volume = {8},
	number = {4},
	year = {2019},
	month = {2019},
	pages = {e1568809},
	abstract = {Immunotherapeutic treatments in head and neck cancer clinical trials include cancer vaccines targeting foreign viral antigens or mutational neoantigens derived from cancer-expressed proteins. Anti-tumor immune responses place cancer cells under selective pressure to lose or downregulate target antigens; therefore, vaccination against virus- or host- "driver" oncogenes are proposed as a strategy to overcome immune escape. Herein, we demonstrate the impact of immunogenic viral antigens on anti-tumor response and immune editing in MOC2-E6E7, a syngeneic murine oral cancer cell line expressing HPV-16 E6 and E7 oncoproteins. Using orthotopic syngeneic models, we observed  tumor growth kinetics of MOC2-E6E7 is delayed in immunocompetent mice compared to parental MOC2 tumors. In contrast, tumor growth remained similar in  mice lacking adaptive immunity. MOC2-E6E7 tumors demonstrated an "inflamed" or immune-activated tumor microenvironment and greater infiltration of CD8 T cells compared to MOC2. By real-time PCR, we detected downregulation of  and  genes in MOC2-E6E7 tumors only in immunocompetent mice, suggesting the loss of ectopic viral antigen expression due to immune editing. We then assessed the efficacy of a biomaterials-based mesoporous silica rod (MSR) cancer vaccine targeting HPV-16 E7 in our model. Vaccination induced robust infiltration of antigen-specific CD8~T cells, which led to tumor growth delay and modestly prolonged survival in MOC2-E6E7 tumors. Increased efficacy was seen in a separate head and neck cancer tumor model, mEER, which obligately expresses E7 antigen. Collectively, our data highlight the need for both immunogenicity and {\textquoteright}driver{\textquoteright} status of target antigens to be considered in cancer vaccine design.},
	issn = {2162-4011},
	doi = {10.1080/2162402X.2019.1568809},
	author = {Dharmaraj, Neeraja and Piotrowski, Stacey L and Huang, Chen and Newton, Jared M and Golfman, Leonard S and Hanoteau, Aurelie and Koshy, Sandeep T and Li, Aileen W and Pulikkathara, Merlyn X and Zhang, Bing and Burks, Jared K and Mooney, David J and Lei, Yu L and Sikora, Andrew G and Young, Simon}
}
