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Inhibition of indoleamine 2,3-dioxygenase 1 synergizes with oxaliplatin for efficient colorectal cancer therapy

We investigated the immunogenic cell death provoked by oxaliplatin (OXA) and the involvement of OXA-induced immunosuppression in colorectal cancer. Immune-proficient or -deficient mice were employed to evaluate the therapeutic effects of OXA. Immunogenic cell death was characterized by cell-surface...

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Autores principales: Miao, Xiaofei, Zhang, Ye, Li, Zengyao, Huang, Longchang, Xin, Taojian, Shen, Renhui, Wang, Tong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889448/
https://www.ncbi.nlm.nih.gov/pubmed/33665222
http://dx.doi.org/10.1016/j.omtm.2020.12.013
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author Miao, Xiaofei
Zhang, Ye
Li, Zengyao
Huang, Longchang
Xin, Taojian
Shen, Renhui
Wang, Tong
author_facet Miao, Xiaofei
Zhang, Ye
Li, Zengyao
Huang, Longchang
Xin, Taojian
Shen, Renhui
Wang, Tong
author_sort Miao, Xiaofei
collection PubMed
description We investigated the immunogenic cell death provoked by oxaliplatin (OXA) and the involvement of OXA-induced immunosuppression in colorectal cancer. Immune-proficient or -deficient mice were employed to evaluate the therapeutic effects of OXA. Immunogenic cell death was characterized by cell-surface calreticulin, cytosol-translocated high migration rate group protein B1 (HMGB1), and secretory ATP content. Bone marrow-derived dendritic cell (BMDC) maturation and CD8(+) T cell expansion were measured by flow cytometry. Expression of immunosuppressive genes was quantified by both RT-PCR and western blots. The proliferative and apoptotic indexes of xenograft tumors were evaluated by immunohistochemistry and TUNEL assays, respectively. The secretory cytokines were measured with ELISA. OXA induced immunogenic cell death of murine colorectal cancer, which greatly depended on the host immune response. OXA-pretreated CT26 cells promoted BMDC maturation and CD8(+) T cell expansion. OXA significantly upregulated indoleamine 2,3-dioxygenase 1 (IDO1) in patient-derived colorectal cancer cells and in combination with the IDO1-specific inhibitor, NLG919, suppressed tumor progression. Simultaneous administration with both OXA and NLG919 greatly promoted CD8(+) T cell infiltration and decreased immunosuppressive cytokine transforming growth factor β (TGF-β) production, whereas increased immunostimulatory cytokines interleukin (IL)-12p70 and interferon (IFN)-γ. We demonstrated the upregulation of IDO1 by OXA, which combined with the IDO1 inhibitor, tremendously potentiated therapeutic effects of OXA against colorectal cancer.
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spelling pubmed-78894482021-03-03 Inhibition of indoleamine 2,3-dioxygenase 1 synergizes with oxaliplatin for efficient colorectal cancer therapy Miao, Xiaofei Zhang, Ye Li, Zengyao Huang, Longchang Xin, Taojian Shen, Renhui Wang, Tong Mol Ther Methods Clin Dev Original Article We investigated the immunogenic cell death provoked by oxaliplatin (OXA) and the involvement of OXA-induced immunosuppression in colorectal cancer. Immune-proficient or -deficient mice were employed to evaluate the therapeutic effects of OXA. Immunogenic cell death was characterized by cell-surface calreticulin, cytosol-translocated high migration rate group protein B1 (HMGB1), and secretory ATP content. Bone marrow-derived dendritic cell (BMDC) maturation and CD8(+) T cell expansion were measured by flow cytometry. Expression of immunosuppressive genes was quantified by both RT-PCR and western blots. The proliferative and apoptotic indexes of xenograft tumors were evaluated by immunohistochemistry and TUNEL assays, respectively. The secretory cytokines were measured with ELISA. OXA induced immunogenic cell death of murine colorectal cancer, which greatly depended on the host immune response. OXA-pretreated CT26 cells promoted BMDC maturation and CD8(+) T cell expansion. OXA significantly upregulated indoleamine 2,3-dioxygenase 1 (IDO1) in patient-derived colorectal cancer cells and in combination with the IDO1-specific inhibitor, NLG919, suppressed tumor progression. Simultaneous administration with both OXA and NLG919 greatly promoted CD8(+) T cell infiltration and decreased immunosuppressive cytokine transforming growth factor β (TGF-β) production, whereas increased immunostimulatory cytokines interleukin (IL)-12p70 and interferon (IFN)-γ. We demonstrated the upregulation of IDO1 by OXA, which combined with the IDO1 inhibitor, tremendously potentiated therapeutic effects of OXA against colorectal cancer. American Society of Gene & Cell Therapy 2021-01-05 /pmc/articles/PMC7889448/ /pubmed/33665222 http://dx.doi.org/10.1016/j.omtm.2020.12.013 Text en © 2021 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Miao, Xiaofei
Zhang, Ye
Li, Zengyao
Huang, Longchang
Xin, Taojian
Shen, Renhui
Wang, Tong
Inhibition of indoleamine 2,3-dioxygenase 1 synergizes with oxaliplatin for efficient colorectal cancer therapy
title Inhibition of indoleamine 2,3-dioxygenase 1 synergizes with oxaliplatin for efficient colorectal cancer therapy
title_full Inhibition of indoleamine 2,3-dioxygenase 1 synergizes with oxaliplatin for efficient colorectal cancer therapy
title_fullStr Inhibition of indoleamine 2,3-dioxygenase 1 synergizes with oxaliplatin for efficient colorectal cancer therapy
title_full_unstemmed Inhibition of indoleamine 2,3-dioxygenase 1 synergizes with oxaliplatin for efficient colorectal cancer therapy
title_short Inhibition of indoleamine 2,3-dioxygenase 1 synergizes with oxaliplatin for efficient colorectal cancer therapy
title_sort inhibition of indoleamine 2,3-dioxygenase 1 synergizes with oxaliplatin for efficient colorectal cancer therapy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889448/
https://www.ncbi.nlm.nih.gov/pubmed/33665222
http://dx.doi.org/10.1016/j.omtm.2020.12.013
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