IDO-vaccine ablates immune-suppressive myeloid populations and enhances anti-tumor effects independent of tumor cell IDO status
Menée à l'aide de modèles murins de tumeurs, cette étude met en évidence l'intérêt d'un vaccin ciblant l'indoléamine-pyrrole 2,3-dioxygénase (IDO) pour supprimer les cellules myéloïdes suppressives et augmenter les effets antitumoraux indépendamment du niveau d'expression de la molécule IDO sur les cellules cancéreuses
The immunosuppressive tumor microenvironment (TME) does not allow generation and expansion of anti-tumor effector cells. One of the potent immunosuppressive factors present in the TME is the indoleamine-pyrrole 2,3-dioxygenase (IDO) enzyme, produced mainly by cancer cells and suppressive immune cells of myeloid origin. In fact, IDO+ myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs) tend to be more suppressive than their IDO¯ counterparts. Hence, therapeutic approaches that would target the IDO+ cells in the TME, while sparing the antigen-presenting functions of IDO¯ myeloid populations, are needed. Using an IDO-specific peptide vaccine (IDO-vaccine), we explored the possibility of generating effector cells against IDO and non-IDO tumor-derived antigens. For this, IDO-secreting (B16F10-melanoma) and non-IDO-secreting (TC-1) mouse tumor models were employed. We showed that IDO-vaccine significantly reduced tumor growth and enhanced survival of mice in both the tumor models, which associated with a robust induction of IDO-specific effector cells in the TME. IDO-vaccine significantly enhanced the anti-tumor efficacy of non-IDO tumor antigen-specific vaccines, leading to an increase in the number of total and antigen-specific activated CD8+ T cells (IFNγ+ and granzyme B+). Treatment with IDO-vaccine significantly reduced the numbers of IDO+ MDSCs and DCs, and immunosuppressive regulatory T cells in both tumor models, resulting in enhanced therapeutic ratios. Together, we showed that vaccination against IDO is a promising therapeutic option for both IDO-producing and non-IDO-producing tumors. IDO-vaccine selectively ablates the IDO+ compartment in the TME, leading to a significant enhancement of the immune responses against other tumor antigen-specific vaccines.