Oncotarget

Research Papers:

Intratumoral depletion of regulatory T cells using CD25-targeted photodynamic therapy in a mouse melanoma model induces antitumoral immune responses

Dong Sun Oh, Heegon Kim, Ji Eun Oh, Hi Eun Jung, Yun Soo Lee, Ji-Ho Park _ and Heung Kyu Lee

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Oncotarget. 2017; 8:47440-47453. https://doi.org/10.18632/oncotarget.17663

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Abstract

Dong Sun Oh1,*, Heegon Kim3,4,*, Ji Eun Oh2, Hi Eun Jung1, Yun Soo Lee3,4, Ji-Ho Park3,4 and Heung Kyu Lee1,2,4

1Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, KAIST, Daejeon, 34141, Republic of Korea

2Graduate School of Medical Science and Engineering, KAIST, Daejeon, 34141, Republic of Korea

3Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of Korea

4KAIST Institute for Health Science and Technology, KAIST, Daejeon, 34141, Republic of Korea

*These authors contributed equally to this work

Correspondence to:

Ji-Ho Park, email: jihopark@kaist.ac.kr

Heung Kyu Lee, email: heungkyu.lee@kaist.ac.kr

Keywords: photodynamic therapy, immunotherapy, Treg, CD25, Chlorin e6

Received: January 06, 2017     Accepted: April 21, 2017     Published: May 07, 2017

ABSTRACT

Tumor immunotherapy aims to overcome the immunosuppressive microenvironment within tumors, and various approaches have been developed. Tumor-associated T regulatory cells (Tregs) suppress the activation and expansion of tumor antigen-specific effector T cells, thus, providing a permissive environment for tumor growth. Therefore, optimal strategies need to be established to deplete tumor-infiltrated Tregs because systemic depletion of Tregs can result in reduced anti-tumor effector cells and autoimmunity. Here, to selectively deplete Tregs in tumors, we intratumorally injected anti-CD25 antibodies conjugated to Chlorin e6 (Ce6), a photosensitizer that absorbs light to generate reactive oxygen species. Local depletion of tumor-associated Tregs with photodynamic therapy (PDT) inhibited tumor growth, which was likely due to the altered tumor immune microenvironment that was characterized by increased infiltration of CD8+ effector T cells and the expression of IFN-γ and CD107a, which is a cytolytic granule exocytosis marker in tumor tissues. Furthermore, PDT-induced intratumoral Treg depletion did not influence adaptive immune responses in a murine influenza infection model. Thus, our results show that intratumoral Treg-targeted PDT could specifically modulate tumor microenvironments by depleting Tregs and could be used as a novel cancer immunotherapy technique.


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