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Udgivet

IDO-vaccine ablates immune-suppressive myeloid populations and enhances anti-tumor effects independent of tumor cell IDO status

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

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  • Rahul Nandre
  • Vivek Verma
  • Pankaj Gaur
  • Veerupaxagouda Patil
  • Xingdong Yang
  • Zainab Ramlaoui
  • Nour Shobaki
  • Mads Hald Andersen
  • Ayako Wakatsuki Pedersen
  • Mai-Britt Zocca
  • Mikayel Mkrtichyan
  • Seema Gupta
  • Samir N Khleif
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The immunosuppressive tumor microenvironment (TME) does not allow generation and expansion of antitumor 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 (MDSC) and dendritic cells (DC) 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 the 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. The IDO vaccine significantly enhanced the antitumor 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 the 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. The 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.

OriginalsprogEngelsk
TidsskriftCancer immunology research
Vol/bind10
Udgave nummer5
Sider (fra-til)571-580
Antal sider10
ISSN2326-6066
DOI
StatusUdgivet - 3 maj 2022

ID: 75713589