Immune profiling of the macroenvironment in colorectal cancer unveils systemic dysfunction and plasticity of immune cells

Haoxian Ke; Peisi Li; Zhihao Li; Xian Zeng; Chi Zhang; Shuzhen Luo; Xiaofang Chen; Xinlan Zhou; Shichen Dong; Shaopeng Chen; Junfeng Huang; Ming Yuan; Runfeng Yu; Shubiao Ye; Tuo Hu; Zhonghui Tang; Dongbin Liu; Kui Wu; Xianrui Wu; Ping Lan

doi:10.1002/ctm2.70175

Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (2) : e70175 DOI: 10.1002/ctm2.70175

RESEARCH ARTICLE

Immune profiling of the macroenvironment in colorectal cancer unveils systemic dysfunction and plasticity of immune cells

Haoxian Ke ¹
, Peisi Li ²^,³
, Zhihao Li ²^,³^,⁴
, Xian Zeng ⁵
, Chi Zhang ²^,³^,⁴
, Shuzhen Luo ⁶^,⁷^,⁸
, Xiaofang Chen ⁶^,⁷^,⁹
, Xinlan Zhou ⁶^,⁷^,⁹
, Shichen Dong ¹⁰^,¹¹
, Shaopeng Chen ²^,³^,⁴
, Junfeng Huang ²^,³^,⁴
, Ming Yuan ²^,³^,⁴
, Runfeng Yu ²^,³^,⁴
, Shubiao Ye ²^,³
, Tuo Hu ²^,³^,⁴
, Zhonghui Tang ⁵
, Dongbin Liu ⁶^,⁷^,⁸
, Kui Wu ⁶^,⁷^,⁸^,^†
, Xianrui Wu ¹^,^†
, Ping Lan ¹^,²^,³^,⁴^,^†

Author information +

¹. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

². Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

³. Biomedical Innovation Center, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

⁴. Department of Colorectal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

⁵. Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

⁶. HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, BGI Research, Hangzhou, China

⁷. Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen, China

⁸. BGI Genomics, Harbin, China

⁹. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

¹⁰. BGI Research, Shenzhen, China

¹¹. Shenzhen Key Laboratory of Single-Cell Omics, BGI Research, Shenzhen, China

wukui@bgi.com

wuxianr5@mail.sysu.edu.cn

lanping@mail.sysu.edu.cn

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Abstract

	•Distinct immunotypes are identified in the CRC macroenvironment.
	•TLS and immunotherapy exert influence on the immune macroenvironment.
	•TLS presence correlates with patient survival, CMS and therapeutic efficacy of ICI.
	•PD-1 and CD69 expressed in CD8+ Tem from blood can predict TLS presence in the CRC macroenvironment.

Keywords

colorectal cancer / single-cell omics / spatial transcription / tumour macroenvironment

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Haoxian Ke,Peisi Li,Zhihao Li,Xian Zeng,Chi Zhang,Shuzhen Luo,Xiaofang Chen,Xinlan Zhou,Shichen Dong,Shaopeng Chen,Junfeng Huang,Ming Yuan,Runfeng Yu,Shubiao Ye,Tuo Hu,Zhonghui Tang,Dongbin Liu,Kui Wu,Xianrui Wu,Ping Lan. Immune profiling of the macroenvironment in colorectal cancer unveils systemic dysfunction and plasticity of immune cells. Clinical and Translational Medicine, 2025, 15(2): e70175 DOI:10.1002/ctm2.70175

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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.