ABSTRACT
BACKGROUND: The role of tumor inflammatory microenvironment in the advancement of cancer, particularly prostate cancer, is widely acknowledged. ELL-associated factor 2 (EAF2), a tumor suppressor that has been identified in the prostate, is often downregulated in prostate cancer. Earlier investigations have shown that mice with EAF2 gene knockout exhibited a substantial infiltration of inflammatory cells into the prostatic stroma. METHODS: A cohort comprising 38 patients who had been diagnosed with prostate cancer and subsequently undergone radical prostatectomy (RP) was selected. These patients were pathologically graded according to the Gleason scoring system and divided into two groups. The purpose of this selection was to investigate the potential correlation between EAF2 and CD163 using immunohistochemistry (IHC) staining. Additionally, in vitro experimentation was conducted to verify the relationship between EAF2 expression, macrophage migration and polarization. RESULTS: Our study demonstrated that in specimens of human prostate cancer, the expression of EAF2 was notably downregulated, and this decrease was inversely associated with the number of CD163-positive macrophages that infiltrated the cancerous tissue. Cell co-culture experiments revealed that the chemotactic effect of tumor cells towards macrophages was intensified and that macrophages differentiated into tumor-associated macrophages (TAMs) when EAF2 was knocked out. Additionally, the application of cytokine protein microarray showed that the expression of chemokine macrophage migration inhibitory factor (MIF) increased after EAF2 knockout. CONCLUSIONS: Our findings suggested that EAF2 was involved in the infiltration of CD163-positive macrophages in prostate cancer via MIF.
ABSTRACT
Allergen-specific immunotherapy (AIT) is the only curative treatment for allergic diseases. However, the long desensitization phase and potentially dangerous allergic side effects limit its broad application. Therefore, safer and more effective vaccines are required. Targeting dendritic cells (DCs) with novel allergen conjugates is a promising strategy for AIT. In this study, a novel vaccine with a DC-targeting effect for AIT was constructed. Liposomes were used as vehicles, and a targeted nanovaccine (Lex-lip-Der f 2) was constructed by loading the recombinant group 2 allergen of Dermatophagoides farinae (Der f 2) and conjugating with the DC-SIGN ligand Lewis X. The effect of the vaccine on DCs and T cell responses and the safety of the vaccine were investigated in vitro. The results showed that the Lex-lip-Der f 2 vaccine was spherical, with size of approximately 128 nm. The protein-loading capacity of the vaccine was 0.106 ± 0.001 mg per mg liposome and protein was gradually released from the liposomes during the first 12 h. Lex-lip-Der f 2 was taken up more efficiently by DCs than non-targeted liposomes or free Der f 2. Besides, Lex-lip-Der f 2 significantly inhibited the release of IL-4, IL-6, and TNF-a from DCs. Accordingly, Der f 2-lip loaded DCs significantly decreased IL-4 levels in autologous naïve CD4+T cells. Moreover, Lex-lip-Der f 2-treated basophils showed lower activation levels. These results suggest that DC-SIGN targeting mediated by Lewis X could inhibit the Th2 cell response and improve vaccine safety, and may be a novel vaccination strategy.