Tumors hijack erythropoiesis for myelopoiesis and immunosuppression
Description
Despite the unprecedented success of immune checkpoint inhibitors (ICIs) as anti-cancer therapy, it remains a prevailing clinical need to identify additional mechanisms underlying ICIs therapeutic efficacy and potential drug resistance. Here, using lineage tracking in cancer patients and tumor-bearing mice, we demonstrate that erythroid progenitor cells lose their developmental potential and switch to the myeloid lineage. Single-cell transcriptome analyses reveal that, notwithstanding quantitative differences in erythroid gene expression, erythroid differentiated myeloid cells (EDMCs) are transcriptionally indistinguishable from their myeloid-originated counterparts. EDMCs possess multifaceted machinery to curtail T cell-mediated anti-tumor responses. Consequently, the EDMCs content within tumor tissues is negatively associated with T cell inflammation for the majority of solid cancers; moreover, EDMCs enrichment, in accordance with anemia manifestation, is predictive of poor prognosis in various cohorts of patients undergoing ICIs therapy. Together, our findings reveal a feed-forward mechanism by which tumors exploit anemia-triggered erythropoiesis for myeloid transdifferentiation and immunosuppression.
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Steps to reproduce
Four independent single cell RNA sequencing were performed by Illumina HiSeq 2500 platform. Raw data were demultiplexed by Cellranger 2.02 and then preprocessed by Seurat v2.34 (all rds files in this folder). A R script (Figure3_fin.R) was provided to reproduce Figure 3.