Dissecting heterogeneity of tumor microenvironment in colorectal cancer using high-resolution single-cell atlas
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Colorectal cancer (CRC) features molecular heterogeneity and differing immune cell infiltration patterns, affecting how patients respond to therapy. However, a comprehensive understanding of immune cell phenotypes across patient subgroups is missing. Here, we dissect the CRC tumor microenvironment by integrating 4,27 million single cells from 1670 samples and 650 patients across 48 studies (76 datasets) representing 7 billion expression values. These samples encompass the full spectrum of disease progression, from normal colon to polyps, primary tumors, and metastases, covering both early and advanced stages of CRC. We present a high-resolution view of CRC with 62 major cell types or states, revealing different cell-type composition patterns in CRC subtypes. The atlas allows for refined tumor classification and patient stratification into four immune phenotypes: immune desert, myeloid, B cell, and T cell subtypes. Using bulk samples with genomic and clinical information, we identify cellular components associated with tumor histology and genotypes. These findings could have important implications for developing improved cancer immunotherapy approaches in CRC.
