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

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.
Publisher
IMPACT JOURNALS LLC
Issue Date
2017-07
Language
English
Keywords

CANCER-IMMUNOTHERAPY; ANTITUMOR IMMUNITY; CD4(+)CD25(+) TREG; SELF-TOLERANCE; CYTOTOXICITY; MICE; PHOTOSENSITIZERS; CARCINOMA; REJECTION; EFFICACY

Citation

ONCOTARGET, v.8, no.29, pp.47440 - 47453

ISSN
1949-2553
DOI
10.18632/oncotarget.17663
URI
http://hdl.handle.net/10203/225223
Appears in Collection
BiS-Journal Papers(저널논문)MSE-Journal Papers(저널논문)
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