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New tools to prevent cancer growth and spread: a 'Clever' approach

Maija Hollmén1, Carlos R Figueiredo1, Sirpa Jalkanen2

  • 1MediCity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland.

British Journal of Cancer
|June 30, 2020
PubMed

Insights

Clever-1 blockade shifts immunosuppressive cells to a pro-inflammatory state, enhancing T-cell responses. This finding is crucial for overcoming immunotherapy resistance in solid tumors.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Clever-1 (Stabilin-1/FEEL-1) is a scavenger receptor on immunosuppressive cells.
  • Clever-1 expression correlates with poor patient outcomes and tumor growth.
  • Its role in immunotherapy resistance and T-cell dysfunction requires further investigation.

Purpose of the Study:

  • To investigate the association between Clever-1 expression and resistance to immune checkpoint therapies.
  • To explore the impact of Clever-1 blockade on T-cell responses and macrophage phenotype in cancer.

Main Methods:

  • Data mining of published human cancer cohorts.
  • Analysis of Clever-1 expression and its correlation with treatment outcomes.
  • Evaluation of Clever-1 blockade effects on immune cell phenotypes.

Main Results:

  • A significant correlation was observed between high Clever-1 positivity and resistance to immune checkpoint therapies.
  • Clever-1 blockade induced a phenotypic switch in macrophages and monocytes from immunosuppressive to pro-inflammatory.
  • This switch was associated with enhanced T-cell responses.

Conclusions:

  • Clever-1 plays a critical role in mediating tumor-induced immunosuppression and immunotherapy resistance.
  • Targeting Clever-1 represents a promising strategy to overcome resistance and enhance anti-tumor immunity.
  • Ongoing clinical trials targeting Clever-1 are supported by these findings.

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