The rapid advancement of single-cell RNA-seq (scRNA-seq) technology has revolutionized our ability to understand cellular composition and cell-type specific transcriptomic characteristics within tumors. In the ten years since the establishment of our group led by Prof. Zemin Zhang, we have dedicated to understanding the heterogeneity of the tumor-infiltrating cells and their interactions within tumor microenvironment. By dissecting the comprehensive tumor-enriched immune cell landscapes[1,2,3,4], our research involves, for example, the illustration of the pro-tumor SPP1+macrophage[5] subset and the activated migratory LAMP3+DC[6] subset. Additionally, we also fousing on identifying novel immunotherapy targets for cancer.

In this study, we integrated single-cell data of colorectal tissues from healthy donors and patients of colitis, polyps and colorectal cancer to identify tumor-specific gene programs and established patient stratification based on different cellular compositions in the tumor microenvironment. The key findings in this study are summarized below.

1. We established a comprehensive single-cell atlas of the human colorectum.
2. We revealed the cellular and transcriptional alteration in immune and non-immune cells.
3. We characterized a rare tumor-specific endothelial cell subset with a potential T cell recruiting role in CRC.
4. We stratify patients into six groups with distinct immune phenotypes. Tumors with distinct TME immune subtypes exploit different immune escape approaches, such as the upregulation of PDL1/2-PDCD1, CD47-SIRPA axes and downregulation of Fc gamma receptors.
5. Stromal cells were major effector cell types of CRC genetic risk genes. 

The findings of this study improve our understanding of colorectal cancer immunology, highlight the necessity of personalized medicine and provide a valuable resource for prioritizing immunotherapy targets for CRC.

Last but not least, this article is the result of a productive collaboration among researchers at Changping Laboratory led by Dr. Sijin Cheng and Prof. Zemin Zhang. Dr. Xiaojing Chu of genetics and computational biology background, Dr. Xiangjie Li, with expertise in bioinformatics and statistics, Yu Zhang, a research assistant in Bioinformatics and others contributed to the projects.

1.Cheng S, Li Z, Gao R, Xing B, Gao Y, Yang Y, Qin S, Zhang L, Ouyang H, Du P, Jiang L, Zhang B, Yang Y, Wang X, Ren X, Bei JX, Hu X, Bu Z, Ji J, Zhang Z. A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells. Cell. 2021 Feb 4;184(3):792-809.e23. doi: 10.1016/j.cell.2021.01.010. PMID: 33545035.
2.Tang F, Li J, Qi L, Liu D, Bo Y, Qin S, Miao Y, Yu K, Hou W, Li J, Peng J, Tian Z, Zhu L, Peng H, Wang D, Zhang Z. A pan-cancer single-cell panorama of human natural killer cells. Cell. 2023 Sep 14;186(19):4235-4251.e20. doi: 10.1016/j.cell.2023.07.034. Epub 2023 Aug 21. PMID: 37607536.
3.Yang Y, Chen X, Pan J, Ning H, Zhang Y, Bo Y, Ren X, Li J, Qin S, Wang D, Chen MM, Zhang Z. Pan-cancer single-cell dissection reveals phenotypically distinct B cell subtypes. Cell. 2024 Jul 16:S0092-8674(24)00712-8. doi: 10.1016/j.cell.2024.06.038. Epub ahead of print. PMID: 39047727.
4.Zheng L, Qin S, Si W, Wang A, Xing B, Gao R, Ren X, Wang L, Wu X, Zhang J, Wu N, Zhang N, Zheng H, Ouyang H, Chen K, Bu Z, Hu X, Ji J, Zhang Z. Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science. 2021 Dec 17;374(6574):abe6474. doi: 10.1126/science.abe6474. Epub 2021 Dec 17. PMID: 34914499.
5.Zhang L, Li Z, Skrzypczynska KM, Fang Q, Zhang W, O'Brien SA, He Y, Wang L, Zhang Q, Kim A, Gao R, Orf J, Wang T, Sawant D, Kang J, Bhatt D, Lu D, Li CM, Rapaport AS, Perez K, Ye Y, Wang S, Hu X, Ren X, Ouyang W, Shen Z, Egen JG, Zhang Z, Yu X. Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer. Cell. 2020 Apr 16;181(2):442-459.e29. doi: 10.1016/j.cell.2020.03.048. PMID: 32302573.
6.Zhang Q, He Y, Luo N, Patel SJ, Han Y, Gao R, Modak M, Carotta S, Haslinger C, Kind D, Peet GW, Zhong G, Lu S, Zhu W, Mao Y, Xiao M, Bergmann M, Hu X, Kerkar SP, Vogt AB, Pflanz S, Liu K, Peng J, Ren X, Zhang Z. Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma. Cell. 2019 Oct 31;179(4):829-845.e20. doi: 10.1016/j.cell.2019.10.003. PMID: 31675496.