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IDO Vaccine Ablates Immune-Suppressive Myeloid Populations and Enhances Antitumor Effects Independent of Tumor Cell IDO Status
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for Cancer Research
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381100/ https://www.ncbi.nlm.nih.gov/pubmed/35290437 http://dx.doi.org/10.1158/2326-6066.CIR-21-0457 |
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author | Nandre, Rahul Verma, Vivek Gaur, Pankaj Patil, Veerupaxagouda Yang, Xingdong Ramlaoui, Zainab Shobaki, Nour Andersen, Mads Hald Pedersen, Ayako Wakatsuki Zocca, Mai-Britt Mkrtichyan, Mikayel Gupta, Seema Khleif, Samir N. |
author_facet | Nandre, Rahul Verma, Vivek Gaur, Pankaj Patil, Veerupaxagouda Yang, Xingdong Ramlaoui, Zainab Shobaki, Nour Andersen, Mads Hald Pedersen, Ayako Wakatsuki Zocca, Mai-Britt Mkrtichyan, Mikayel Gupta, Seema Khleif, Samir N. |
author_sort | Nandre, Rahul |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9381100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for Cancer Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-93811002023-01-05 IDO Vaccine Ablates Immune-Suppressive Myeloid Populations and Enhances Antitumor Effects Independent of Tumor Cell IDO Status Nandre, Rahul Verma, Vivek Gaur, Pankaj Patil, Veerupaxagouda Yang, Xingdong Ramlaoui, Zainab Shobaki, Nour Andersen, Mads Hald Pedersen, Ayako Wakatsuki Zocca, Mai-Britt Mkrtichyan, Mikayel Gupta, Seema Khleif, Samir N. Cancer Immunol Res Research Articles 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. American Association for Cancer Research 2022-05-03 2022-03-15 /pmc/articles/PMC9381100/ /pubmed/35290437 http://dx.doi.org/10.1158/2326-6066.CIR-21-0457 Text en ©2022 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
spellingShingle | Research Articles Nandre, Rahul Verma, Vivek Gaur, Pankaj Patil, Veerupaxagouda Yang, Xingdong Ramlaoui, Zainab Shobaki, Nour Andersen, Mads Hald Pedersen, Ayako Wakatsuki Zocca, Mai-Britt Mkrtichyan, Mikayel Gupta, Seema Khleif, Samir N. IDO Vaccine Ablates Immune-Suppressive Myeloid Populations and Enhances Antitumor Effects Independent of Tumor Cell IDO Status |
title | IDO Vaccine Ablates Immune-Suppressive Myeloid Populations and Enhances Antitumor Effects Independent of Tumor Cell IDO Status |
title_full | IDO Vaccine Ablates Immune-Suppressive Myeloid Populations and Enhances Antitumor Effects Independent of Tumor Cell IDO Status |
title_fullStr | IDO Vaccine Ablates Immune-Suppressive Myeloid Populations and Enhances Antitumor Effects Independent of Tumor Cell IDO Status |
title_full_unstemmed | IDO Vaccine Ablates Immune-Suppressive Myeloid Populations and Enhances Antitumor Effects Independent of Tumor Cell IDO Status |
title_short | IDO Vaccine Ablates Immune-Suppressive Myeloid Populations and Enhances Antitumor Effects Independent of Tumor Cell IDO Status |
title_sort | ido vaccine ablates immune-suppressive myeloid populations and enhances antitumor effects independent of tumor cell ido status |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381100/ https://www.ncbi.nlm.nih.gov/pubmed/35290437 http://dx.doi.org/10.1158/2326-6066.CIR-21-0457 |
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