Depleting Tumor-Associated Tregs Via Nanoparticle-Mediated Hyperthermia to Enhance Anti-CTLA-4 Immunotherapy

Abstract

Aim: We aim to demonstrate that a local nanoparticle-mediated hyperthermia can effectively eliminate tumor-associated Tregs and thereby boost checkpoint blockade-based immunotherapy. Materials & methods: Photothermal therapy (PTT), mediated with systemically administered stealthy iron-oxide nanoparticles, was applied to treat BALB/c mice bearing 4T1 murine breast tumors. Flow cytometry was applied to evaluate both Treg and CD8+ T-cell population. Tumor growth following combination therapy of both PTT and anti-CTLA-4 was further evaluated. Results: Our data reveal that tumor-associated Tregs can be preferentially depleted via iron-oxide nanoparticles-mediated PTT. When combining PTT with anti-CTLA-4 immunotherapy, we demonstrate a significant inhibition of syngeneic 4T1 tumor growth. Conclusion: This study offers a novel strategy to overcome Treg-mediated immunosuppression and thereby to boost cancer immunotherapy.

Photothermal therapies to improve immune checkpoint blockade for cancer

“…On the contrary, there was no decrease in tumor growth (similar growth as untreated tumors) with aCTLA-4 treatment alone. This combination treatment strategy also offered longterm immunological memory as illustrated by 66.6% tumorfree survival (8/12 animals) of rechallenged animals, demonstrating successful combination of PTT and ICB therapy [70].…”

“…Recently, Chen et al illustrated the role of Tregs in the efficacy of IONPs-PTT in combination with aCTLA-4 ICB in a 4T1 breast cancer model in BALB/c mice [70]. Tregs are an important subset of TILs with higher expression of CTLA-4 [94] and are often associated with poor prognosis in a wide variety of cancers [95].…”

Advances in Magnetic Nanoparticle‐Mediated Cancer Immune‐Theranostics

“…Sun et al used stealthy IONP to deplete tumor-associated Tregs by PTT to enhance anti-CTLA4 immunotherapy. [101] In combination with CTLA4 antibody, a single administration of IONP plus PTT could eliminate the primary tumor, but the population of Treg did not decrease. In contrast, a significant reduction of Tregs was observed for the treatment that involved two PTT at 1 day interval.…”

Tumor Targeted Nanocarriers for Immunotherapy

“…The combined treatment with these IMT-loaded nanocarriers and anti-CTLA-4 induced a selective T reg depletion in melanoma-bearing mice, which reverted the immunosuppressive environment leading to a higher CD8+ T cells accumulation and activation in the tumoral tissue. Chen and co-workers have employed small polymer-coated iron oxide nanoparticles (around 30 nm of diameter) to destroy Treg in breast tumor murine models by photothermal therapy (PTT) [95]. It is worthy to point out here the difference between PDT, which employs photosensitizers to produce ROS in the presence of certain light wavelengths and PTT, that provoke a temperature increase in the tissue without generating ROS.…”