Single-Cell RNA Sequencing Reveals Immuno-Oncology Characteristics of Tumor-Infiltrating T Lymphocytes in Photodynamic Therapy-Treated Colorectal Cancer Mouse Model

Author:

Lee Eun-Ji1ORCID,Choi Jang-Gi1ORCID,Han Jung Ho1ORCID,Kim Yong-Wan2,Lim Junmo2,Chung Hwan-Suck13ORCID

Affiliation:

1. Korean Medicine Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea

2. Dongsung Cancer Center, Dongsung Biopharmaceutical, Daegu 41061, Republic of Korea

3. Korean Convergence Medical Science Major, University of Science and Technology (UST), KIOM Campus, Daegu 41062, Republic of Korea

Abstract

Photodynamic therapy (PDT) has shown promise in reducing metastatic colorectal cancer (CRC); however, the underlying mechanisms remain unclear. Modulating tumor-infiltrating immune cells by PDT may be achieved, which requires the characterization of immune cell populations in the tumor microenvironment by single-cell RNA sequencing (scRNA-seq). Here, we determined the effect of Chlorin e6 (Ce6)-mediated PDT on tumor-infiltrating T cells using scRNA-seq analysis. We used a humanized programmed death-1/programmed death ligand 1 (PD-1/PD-L1) MC38 cell allograft mouse model, considering its potential as an immunogenic cancer model and in combination with PD-1/PD-L1 immune checkpoint blockade. PDT treatment significantly reduced tumor growth in mice containing hPD-1/PD-L1 MC38 tumors. scRNA-seq analysis revealed that the PDT group had increased levels of CD8+ activated T cells and CD8+ cytotoxic T cells, but decreased levels of exhausted CD8+ T cells. PDT treatment also enhanced the infiltration of CD8+ T cells into tumors and increased the production of key effector molecules, including granzyme B and perforin 1. These findings provide insight into immune-therapeutic modulation for CRC patients and highlight the potential of PDT in overcoming immune evasion and enhancing antitumor immunity.

Funder

Korea Institute of Oriental Medicine

Ministry of Science and ICT

National Research Council of Science & Technology

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Single-cell multi-omics in the study of digestive system cancers;Computational and Structural Biotechnology Journal;2024-12

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