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Engineered Hybrid Treg-Targeted Nanosomes Restrain Lung Immunosuppression by Inducing Intratumoral CD8+T Cell
Kalliopi Domvri1, Savvas Petanidis2,3, Paul Zarogoulidis4
1Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, 57010, Greece.
International Journal of Nanomedicine
|September 29, 2022
Summary
This study developed Treg-targeted nanocarriers (NCs) to combat immunosuppression in metastatic lung cancer. The nanotherapy effectively reduced tumor volume and activated anti-tumor immunity, offering a promising strategy for cancer treatment.
Area of Science:
- Nanomedicine and Cancer Immunotherapy
- Tumor Microenvironment Modulation
Background:
- Metastatic lung cancer immunotherapy faces challenges due to regulatory T cell (Treg)-mediated immunosuppression and tumor relapse.
- Existing immunotherapy regimes show limited efficacy in metastatic lung cancer, necessitating novel therapeutic approaches.
Purpose of the Study:
- To design and evaluate biocompatible Treg-targeted nanocarriers (NCs) for immune-based nanotherapy.
- To inhibit and reverse Treg-related immunosuppression within the lung tumor microenvironment.
- To explore the anti-tumor effects of NCs combining Dasatinib and Epacadostat in vitro and in vivo.
Main Methods:
- Development of biodegradable nanosomes encapsulating Dasatinib and Epacadostat for Treg targeting.
- In vitro and in vivo evaluation using flow cytometry, immunofluorescence, PET/CT, PTT/PA imaging, and a Balb/c tumor model.
- Assessment of anti-tumor effects, immune cell populations, cytokine expression, and therapeutic efficacy in metastatic breast cancer models.
Main Results:
- NC treatment induced significant tumor cell apoptosis, reduced tumor volume, and decreased Ki-67 expression.
- Enhanced drug circulation time and accumulation in lung and peripheral tissues were observed.
- Increased intratumoral Th1 cytokines (TNF-α, IL-12, IL-6), mature dendritic cells, and T cell enrichment, alongside reduced myeloid-derived suppressor cells (MDSCs).
- Photothermal therapy (PTT) with NCs demonstrated efficient tumor ablation and long-term tumor control when combined with PD-L1 blockade.
Conclusions:
- The developed nano-enabled platform effectively inhibits Treg-dependent immunosuppression in non-small cell lung cancer (NSCLC).
- This nanotherapeutic strategy shows significant potential for treating metastatic neoplasia.
- Combination therapy with photothermal and checkpoint blockade offers durable tumor control.
