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

AI Article Synopsis

  • Tumor immunotherapy seeks to counteract the immune suppression caused by tumors, particularly through targeting T regulatory cells (Tregs) that inhibit tumor-fighting T cells.
  • A strategy using anti-CD25 antibodies linked to a photosensitizer (Chlorin e6) was developed to selectively eliminate Tregs within tumors through photodynamic therapy (PDT).
  • This Treg depletion led to reduced tumor growth by enhancing the presence of active CD8+ T cells and specific immune markers in the tumor, suggesting that PDT could be a promising new approach in cancer treatment without negatively affecting the broader immune response.

Article 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564577PMC
http://dx.doi.org/10.18632/oncotarget.17663DOI Listing

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