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Related Concept Videos

Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...

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Region-Specific CD16+ Neutrophils Promote Colorectal Cancer Progression by Inhibiting Natural Killer Cells.

Yan Zhang1,2, Zien Wang1,2, Yu Lu1

  • 1State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|May 25, 2024
PubMed
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Researchers discovered CD16+ neutrophils in colorectal cancer (CRC) tumors that promote cancer by harming natural killer (NK) cells. Targeting these neutrophils could offer new CRC diagnostics and therapies.

Keywords:
CRCNETNK cellcholesterolneutrophil

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Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • The colon hosts a significant immune presence, yet innate immune responses in colorectal cancer (CRC) are not fully understood.
  • Understanding how innate immune cells are activated is crucial for developing effective CRC treatments.

Purpose of the Study:

  • To identify and characterize innate immune cells involved in colorectal cancer progression.
  • To elucidate the mechanisms by which these cells influence the tumor microenvironment and impact anti-tumor immunity.

Main Methods:

  • Utilized imaging mass cytometry (IMC), immunofluorescence, and flow cytometry to identify specific neutrophil populations in CRC tissues.
  • Investigated the molecular pathways, including the CD16/TAK1/NF-κB axis, involved in neutrophil function and cholesterol metabolism.
  • Assessed the impact of CD16+ neutrophils on natural killer (NK) cell activity and tumor progression.

Main Results:

  • Identified a distinct population of CD16+ neutrophils that accumulate in CRC tumors and exhibit pro-tumor activity.
  • Found that these neutrophils have abnormal cholesterol accumulation, driven by the CD16/TAK1/NF-κB pathway, upregulating scavenger receptors (CD36, LRP1).
  • Demonstrated that CD16+ neutrophils impair NK cell function by inhibiting cholesterol uptake, disrupting lipid raft formation, and inducing NK cell death via neutrophil extracellular traps (NETs).

Conclusions:

  • CRC-associated CD16+ neutrophils possess pro-tumor functions by suppressing NK cell-mediated anti-tumor immunity.
  • These neutrophils represent a potential diagnostic biomarker for CRC.
  • Targeting CD16+ neutrophils offers a promising therapeutic strategy for colorectal cancer treatment.