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表征和评估不同疗法塑造的结直肠癌免疫微环境格局

Characterising and Evaluating the Immune Microenvironment Landscapes of Colorectal Cancer Shaped by Different Therapies.

作者信息

Zhou Chen, Wang Yifan, Li Yuanyuan, Zhang Weitao, Bai Yunmeng

机构信息

Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.

School of Medicine, Southern University of Science and Technology, Shenzhen, China.

出版信息

IET Syst Biol. 2025 Jan-Dec;19(1):e70028. doi: 10.1049/syb2.70028.

Abstract

Colorectal cancer (CRC) occurs as the third most common cancer with high mortality across the world. Understanding the intratumoral immune cell heterogeneity and their responses to various therapies is crucial for enhancing patient outcomes. This study aimed to characterise and evaluate the immune microenvironment landscapes of CRC shaped by different therapies including CD73 inhibitor, PD-1 blockade and photothermal therapy (PTT). Our investigation revealed that three therapies could commonly modulate the down-regulation of Treg, M2 macrophage and Ptprj+ G4 granulocyte, up-regulation of effector/memory T cell, M1 macorphage and Hilpda+ G1 granulocyte. Moreover, we identified the uniquely dis-regulated cell types and pathway activities response to each therapy, such as CD73 inhibitor enriched more Cd8+ memory and central memory (CM) cell, PD-1 blockade with more Cd8+ CTL and Cxcl3+ G2 granulocyte, and PTT with more Cd8+ effector memory and Rethlg+ G3 granulocyte cell. These responses disordered the glycolysis, angiogenesis, phagocytosis functions and cellular communication to reshape the CRC tumour immune microenvironment. We provide the detail insights into the intratumoral immunomodulation preferences of CRC mice treated with CD73 inhibitor, PD-1 blockade and PTT therapies, which might contribute to the ongoing development of more effective anticancer strategies.

摘要

结直肠癌(CRC)是全球第三大常见癌症,死亡率很高。了解肿瘤内免疫细胞的异质性及其对各种治疗的反应对于提高患者预后至关重要。本研究旨在表征和评估由不同疗法(包括CD73抑制剂、PD-1阻断和光热疗法(PTT))塑造的CRC免疫微环境格局。我们的研究表明,三种疗法通常可以调节Treg、M2巨噬细胞和Ptprj+ G4粒细胞的下调,效应/记忆T细胞、M1巨噬细胞和Hilpda+ G1粒细胞的上调。此外,我们确定了每种疗法独特的失调细胞类型和通路活性反应,例如CD73抑制剂富集更多的Cd8+记忆和中央记忆(CM)细胞,PD-1阻断富集更多的Cd8+ CTL和Cxcl3+ G2粒细胞,PTT富集更多的Cd8+效应记忆和Rethlg+ G3粒细胞。这些反应扰乱了糖酵解、血管生成、吞噬功能和细胞通讯,从而重塑了CRC肿瘤免疫微环境。我们详细深入地了解了用CD73抑制剂、PD-1阻断和PTT疗法治疗的CRC小鼠的肿瘤内免疫调节偏好,这可能有助于正在进行的更有效抗癌策略的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f22/12266622/2f92cc62dde7/SYB2-19-e70028-g008.jpg

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