CTSB+ macrophage repress memory immune hub in the liver metastasis site of colorectal cancer patient revealed by multi-omics analysis

Biochem Biophys Res Commun. 2022 Oct 20:626:8-14. doi: 10.1016/j.bbrc.2022.06.037. Epub 2022 Jul 3.

Abstract

Colorectal cancer (CRC) is a lethal malignant tumor and 25-30% of CRC patients develop liver metastasis (LM) with a worse prognosis, but the metastasis mechanism is yet elucidated. To identify the potential immune regulatory mechanism of CRC liver metastasis, single-cell sequencing and multiplex immunohistochemistry were applied to identify key cell populations of the tumor microenvironment (TME) in the CRC and LM sites. We found memory CD8+ T cells, B cells, and CTSB + macrophages were enriched in the LM site, forming the memory immune hub, which was important for the anti-tumor response against LM. Therefore, our results revealed that memory immune responses were called in the LM sites and probably meditated by CTSB + macrophages.

Keywords: CTSB+ macrophage; Colorectal cancer; Liver metastasis; Multi-omics analysis; Suppressive immune hub.

MeSH terms

  • CD8-Positive T-Lymphocytes / pathology
  • Cathepsin B
  • Colorectal Neoplasms* / pathology
  • Humans
  • Liver Neoplasms* / secondary
  • Macrophages / pathology
  • Tumor Microenvironment

Substances

  • CTSB protein, human
  • Cathepsin B