Intratumoral depletion of regulatory T cells using CD25-targeted photodynamic therapy induces anti-tumoral immune responses

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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 deplete Tregs selectively 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 by 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 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. Keywords: Photodynamic therapy, Treg, CD25, Chlorin e6
Publisher
INTERNATIONAL CANCER IMMUNOTHERAPY CONFERENCE
Issue Date
2018-09-30
Language
English
Citation

CRI-CIMT-EATI-AACR FOURTH INTERNATIONAL CANCER IMMUNOTHERAPY CONFERENCE

URI
http://hdl.handle.net/10203/249411
Appears in Collection
MSE-Conference Papers(학술회의논문)BiS-Conference Papers(학술회의논문)
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