Screening and Identification of Prognostic Tumor-Infiltrating Immune Cells and Genes of Endometrioid Endometrial Adenocarcinoma: Based on The Cancer Genome Atlas Database and Bioinformatics.

BACKGROUND: Endometrioid endometrial adenocarcinoma (EEA) is one of the most common tumors in the female reproductive system. With the further understanding of immune regulation mechanism in tumor microenvironment, immunotherapy is emerging in tumor treatment. However, there are few systematic studies on EEA immune infiltration. METHODS: In this study, prognostic tumor-infiltrating immune cells (TIICs) and related genes of EEA were comprehensively analyzed for the first time through the bioinformatics method with CIBERSORT algorithm as the core. Gene expression profile data were downloaded from the TCGA database, and the abundance ratio of TIICs was obtained. Kaplan-Meier analysis and Cox regression analysis were used to identify prognostic TIICs. EEA samples were grouped according to the risk score in Cox regression model. Differential analysis and functional enrichment analyses were performed on high- and low-risk groups to find survival-related hub genes, which were verified by Tumor Immune Estimation Resource (TIMER). RESULT: Four TIICs including memory CD4+ T cells, regulatory T cells, natural killer cells and dendritic cells were identified. And two hub gene modules were found, in which six hub genes including APOL1, CCL17, RBP4, KRT15, KRT71, and KRT79 were significantly related to overall survival and were closely correlated with some certain TIICs in the validation of TIMER. CONCLUSION: In this study, four prognostic TIICs and six hub genes were found to be closely related to EEA. These findings provided new potential targets for EEA immunotherapy.

Evaluation of immune responses induced by a novel human papillomavirus type 16 E7 peptide-based vaccine with Candida skin test reagent as an adjuvant in C57BL/6 mice.

Cell mediated immune (CMI) responses are crucial for the clearance of human papillomavirus (HPV) infection and HPV-associated lesions. Activated CD8 T cells are critical effector cells in recognizing and killing HPV-infected or HPV-transformed cells. CD4 T cells provide help for priming the generation and maintenance of CD8 T cells as well as for tumors immunity. An ideal therapeutic HPV peptide-based vaccine should induce both a robust CD8 T-cell response as well as a CD4 T-cell response for ensuring their efficiency. Candida skin test reagent was demonstrated to be able to induce the secretion of IL-12 by Langerhans cells and T-cell proliferation in vitro by our group, which indicated the potential of Candida to enhance CMI response. In this current study, we designed a novel HPV peptide-based vaccine which includes HPV16 E7 peptides and Candida as an adjuvant. The immune responses induced by the vaccine were comprehensively evaluated. The results showed that the vaccine induced significant HPV-specific CD8 T-cell and Th1 CD4 T-cell responses as well as humoral immune response. It is interesting that Candida alone induced a significant polarization of Th1 response an production of IFN-γ, which indicated Candida alone may be used as a potential immunotherapeutic reagent not only for HPV-associated lesions but also for other viral infection or even cancers.