Journal
ONCOTARGET
Volume 8, Issue 29, Pages 47440-47453Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.17663
Keywords
photodynamic therapy; immunotherapy; Treg; CD25; Chlorin e6
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Funding
- National Research Foundation [NRF-2016R1A2B2015028, NRF-2015R1A4A1042416, NRF-2014M3A9A5044964, NRF-2012M3A9B4028274]
- KAIST Future Systems Healthcare Project - Ministry of Science, ICT, and Future Planning of Korea
- Basic Science Research Program through the National Research Foundation - Ministry of Science, ICT & Future Planning, Republic of Korea [NRF-2015R1A1A1A05001420]
- KAIST KI Convergence Project for Health Science and Technology
- National Research Foundation of Korea [2012M3A9B4028274] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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-gamma 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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