单细胞 RNA 测序揭示光动力治疗结直肠癌小鼠模型中肿瘤浸润 T 淋巴细胞的免疫肿瘤学特征

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.