Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer.
By Lei Zhang, Ziyi Li, Katarzyna M. Skrzypczynska, Qiao Fang, Wei Zhang, Sarah A. O’Brien, Yao He, Lynn Wang, Qiming Zhang, Aeryon Kim and 19 more. Cell, 2020
1,283 citations recorded by the source corpus.
Single-cell RNA sequencing (scRNA-seq) is a powerful tool for defining cellular diversity in tumors, but its application toward dissecting mechanisms underlying immune-modulating therapies is scarce. We performed scRNA-seq analyses on immune and stromal populations from colorectal cancer patients, identifying specific macrophage and conventional dendritic cell (cDC) subsets as key mediators of cellular cross-talk in the tumor microenvironment. Defining comparable myeloid populations in mouse tumors enabled characterization of their response to myeloid-targeted immunotherapy. Treatment with anti-CSF1R preferentially depleted macrophages with an inflammatory signature but spared macrophage populations that in mouse and human expresses pro-angiogenic/tumorigenic genes. Treatment with a CD40 agonist antibody preferentially activated a cDC population and increased Bhlhe40+ Th1-like cells and CD8+ memory T cells. Our comprehensive analysis of key myeloid subsets in human and mouse identifies critical cellular interactions regulating tumor immunity and defines mechanisms underlying myeloid-targeted immunotherapies currently undergoing clinical testing.
Subfields: Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/8a107f4a6936ef07cdae0cef2e4e2ef81262b426
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Citations in the corpus
- The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications (2020, background): “Importantly, they suggested that the depletion of specific TAM subsets could contribute to the improvement of myeloid-targeted immunotherapies and could achieve synergistic effects when combined with ICB therapies.(212) These discoveries uncover the interplay between innate and adaptive immunity and”
- Spatiotemporal analysis of human intestinal development at single-cell resolution (2021, background): “…described gene identifying polarize macrophages termed SPP1+Macrophages (Zhang et al., 2017), and the second expressed genes involved in complement formation (C1QA, C1QC) and IL1B at a higher level – in keepingwith a classically activated (M1) phenotype (Azizi et al., 2018; Zhang et al., 2020).”