IDO Vaccine Ablates Immune-Suppressive Myeloid Populations and Enhances Antitumor Effects Independent of Tumor Cell IDO Status

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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)571-580
Number of pages10
JournalCancer Immunology Research
Volume10
Issue number5
DOIs
StatePublished - May 2022

Bibliographical note

Funding Information:
We are grateful to Jeannie and Tony Loop for their generous support to SNK’s laboratory. We acknowledge the Flow Cytometry & Cell Sorting Shared Resource in Georgetown University, which is partially supported by NIH/NCI grant P30-CA051008 and NIH S10 grant, S10OD016213.

Funding Information:
M.H. Andersen reports personal fees from IO Biotech during the conduct of the study; grants and personal fees from IO Biotech outside the submitted work; in addition, M.H. Andersen has a patent for INDOLEAMINE 2,3-DIOXYGENASE BASED IMMUNOTHERAPY issued. A.W. Pedersen reports other support from IO Biotech ApS during the conduct of the study; other support from IO Biotech ApS outside the submitted work. M.-B. Zocca reports personal fees and other support from IO Biotech during the conduct of the study; personal fees from Valo Therapeutics outside the submitted work. S.N. Khleif reports grants and other support from

Publisher Copyright:
© 2022 The Authors

Keywords

  • Animals
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Melanoma/drug therapy
  • Mice
  • Tumor Microenvironment

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural

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