Deciphering single-cell transcriptomic landscape of tumors in colorectal cancer treated with photothermal semiconducting polymers to design the combination therapy with checkpoint blockades for inhibition of tumor progression and metastasis

作者：Haitao Yuan, Yunmeng Bai, Di Gu, Peili Wang, Xin Sun, Jing Yang, Yin Kwan Wong, Wei Huang, Xiaoxian Wang, Jingbo Ma, Zhiyu Dong, Ruixing Chen, Jiexuan Li, Zhijie Li, Guo-hua Zeng, Zipeng Gong, Chuanbin Yang, Jigang Wang · 发表于：Nano Today · 年份：2024 · DOI：10.1016/j.nantod.2024.102419 · 被引用次数：7 · 研究领域：Immunotherapy and Immune Responses、Nanoplatforms for cancer theranostics、Cancer Immunotherapy and Biomarkers

Immunotherapy is often less effective for tumors with “immune-excluded,” or “immune-desert” microenvironment. To circumvent this hurdle, new therapeutic strategies need to be designed to reprogram the tumor microenvironment (TME). It is well known that photothermal therapy (PTT) can prime the TME and provoke the systemic anti-tumor immunity. But few studies perform extensive exploration in depth to decipher the changes in TME after PTT with cutting-edge technology besides conventional flow cytometry analysis. In this study, we designed a nanosystem consisting of organic semiconductor polymer liposome nanoparticles (Y8 NPs) as a multimodal imaging and photothermal agent to image and treat tumors. Upon laser irradiation, Y8 NPs in tumors could rapidly increase the temperature, induce massive cancer cell apoptosis and also promote the immunogenic cell death (ICD), ultimately remodulating the TME. We employed single cell RNA sequencing (scRNA-seq) technology to comprehensively explore transcriptomic profiling of individual cells constituting TME, demonstrating heterogenous alterations in the subtypes of immune cells, even tumor cells. Considering the findings by scRNA-seq and TME remodulation, the combinational strategy with checkpoint blockade PD-1 antibody was designed to treat the tumors, demonstrating that the combination not only impedes primary tumor progression but also produce profound abscopal anti-tumor effect. In conclusion, we provide a simple strategy for the remodul...