Depletion of tumor-associated macrophages enhances the anti-tumor immunity induced by a Toll-like receptor agonist-conjugated peptide.

摘要: It has been reported that lipopeptides can be used to elicit cytotoxic T lymphocyte (CTL) responses against viral diseases and cancer. In our previous study, we determined mono-palmitoylated peptides enhance anti-tumor in the absence of adjuvant activity. To investigate whether di-palmitoylated with TLR2 agonist activity are able induce immunity, synthesized a di-palmitic acid-conjugated long peptide contains murine CTL epitope HPV E749–57 (Pam2IDG). Pam2IDG stimulated maturation bone marrow-derived dendritic cells (BMDCs) through TLR2/6. After immunization, induced higher levels cell than those obtained its non-lipidated counterpart (IDG). prophylactic model, immunization completely inhibited tumor growth, whereas IDG was unable inhibit growth. However, could not effectively growth established tumors. Therefore, further investigated depletion immunosuppressive factors improve therapeutic effects Pam2IDG. Our data indicate treatment combined clodronate/liposome delays increases survival rate. We also observed improved by diminishing function tumor-associate macrophages (TAMs) use an IL10 receptor blocking antibody or Cyclooxygenase 2 (Cox-2) inhibitor. conclusion, TAMs may immunity agonist-conjugated peptide.