Host Basal Immune Response Type is a Determinination Factor for PRSS14/Epithin Peptide Vaccine against Breast Cancer Metastasis

초록

Background: PRSS14/Epithin plays important roles in EMT, angiogenesis, transendothelial cell migration and is particularly upregulated in ER- breast cancer patients. C57BL/6 and Balb/c mouse strains are TH1 and TH2 dominant, respectively. Host immune response types can be modulated by various adjuvants. EpCAM is a useful marker for epithelial cancer detection. Method: Two orthotopic injection of breast cancer cells (4T1 and EO771) into syngenic hosts (C57BL/6 and Balb/c) and one transgenic mouse model (MMTV-PyMT) were tested for the peptide cancer vaccine using peptides derived from PRSS14/epithin. Survival curves, tumor sizes and metastasis nodules were monitored. Response to vaccine was screened by isotyping specific antibodies to the vaccine and by analyzing immune cells in tumor tissues using flow cytometry. Results: Immunizing with KLH conjugated peptide vaccine in three mouse models all increased survival, reduced tumor sizes, and abrogated metastasis. Host mice produced sequence specific antibodies of both TH1 and/or TH2 depending on the types of adjuvants in host animals. MMTV-PyMT mice showed bidirectional vaccine effects: reduced tumor growth and metastasis only with CFA/IFA, but adverse endpoints with Alum adjuvant. However, beneficial vaccine effect was correlated only with TH2 type antibody, not with TH1, even in the case of vaccine with CFA/IFA. In addition, the presence of eosinophils in the tumor tissue showed strong correlation with positive vaccine effects, indicating host innate immune system significantly contribute in managing breast cancer in addition to Ag specific response. These results indicated that the host basal TH- types are critical for the vaccine against metastatic breast cancer. Moreover, we found the tumor tissue in vaccinated mice showed decrease in proportions of EpCAMlow cells. Conclusion: PRSS14/epithin derived specific peptide vaccine can be useful in reduction of the size of cancer and metastasis when it is combine