Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer
Menée à partir de l'analyse du transcriptome de 91 103 cellules cancéreuses issues de 23 patients coréens et de 6 patients belges atteints d'un cancer colorectal, cette étude met en évidence une association entre les caractéristiques génétiques des cellules cancéreuses et les caractéristiques du micro-environnement immunitaire
Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,103 unsorted single cells from 23 Korean and 6 Belgian patients. Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. Intercellular network reconstruction supported the association between cancer cell signatures and specific stromal or immune cell populations. Our collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.
Nature Genetics , résumé, 2020