Temporary elimination of IL-10 enhanced the effectiveness of cyclophosphamide and BMDC-based therapy by decrease of the suppressor activity of MDSCs and activation of antitumour immune response
PBN-AR
Instytucja
Instytut Immunologii i Terapii Doświadczalnej im. Ludwika Hirszfelda Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
EN
Czasopismo
Immunobiology
ISSN
0171-2985
EISSN
1878-3279
Wydawca
Amsterdam : Elsevier
Rok publikacji
2015
Numer zeszytu
3
Strony od-do
389-398
Numer tomu
220
Identyfikator DOI
Liczba arkuszy
Słowa kluczowe
EN
Anti-IL-10 antibodies
Antitumour chemoimmunotherapy
Cyclophosphamide
Dendritic cells
Experimental MC38 colon carcinoma
Myeloid derived suppressor cells
Streszczenia
Język
EN
Treść
The antitumour activity of the dendritic cell (DC)-based cellular vaccines is greatly reduced in hostile tumour microenvironment. Therefore, there are many attempts to eliminate or neutralize both suppressor cells and cytokines. The aim of the investigation was to verify if temporary elimination of IL-10 just before injection of bone marrow-derived DCs (BMDCs) enhance the antitumour activity of applied vaccines and help to overcome the immunosuppressive tumour barrier. Mice bearing colon carcinoma MC38 were given single dose of cyclophosphamide (CY) followed by alternate injections of anti-IL-10 antibodies and BMDC-based vaccines consisted of BMDCs stimulated with MC38 tumour antigen (BMDC/TAg) or the combination of BMDC/TAg with BMDCs transduced with IL-12 genes (BMDC/IL-12). The high tumour growth inhibition was observed in mice treated with CY + anti-IL-10 + BMDC/TAg as well as CY ± anti-IL-10 + BMDC/TAg + BMDC/IL-12. However, the mechanisms of action of particular treatment schemes were diversified. Generally, it was observed that application of anti-IL-10 Abs reduced suppressor activity of myeloid-derived suppressor cells (MDSCs). However, anti-IL-10 Abs in combination with diversely composed BMDC-based vaccines induced different components of an antitumour response. The high cytotoxic activity of spleen-derived NK cells and increased influx of these cells into tumours of mice treated with CY + anti-IL-10 + BMDC/TAg indicate that mice from the group developed strong NK-dependent response. Whereas, application of anti-IL-10 Abs just before injection of BMDC/TAg + BMDC/IL-12 did not enhanced NK cell activity. Furthermore, it significantly impaired effectiveness of therapy composed of CY + BMDC/TAg + BMDC/IL-12 vaccine in induction of Th1 type immune response. Taken together, our results indicate that temporary elimination of IL-10 is an important and effective way to decrease the immune suppression associated with MDSCs activity and represents a useful strategy for successful enhancement of the antitumour activity of BMDC/TAg-based vaccines.
Cechy publikacji
artykuł oryginalny
Inne
System-identifier
PX-56b48bcc8106eb71826f827f
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