The pro-tumor effect of CD200 expression is not mimicked by agonistic CD200R antibodies

Zofia Pilch1, Katarzyna Tonecka1, Marcin Skorzynski1

  • 1Department of Immunology, Medical University of Warsaw, Warsaw, Poland.

Plos One
|January 18, 2019
PubMed

Insights

Blocking the CD200 ligand, not activating its receptor (CD200R), reduced melanoma tumor growth. This highlights CD200 as a potential therapeutic target in cancer immunotherapy.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Tumor-infiltrating immune cells influence cancer progression.
  • The CD200 receptor (CD200R) pathway, which inhibits myeloid cell activation, has complex roles in tumor growth.
  • Previous studies show both reduced tumor growth and tumorigenic effects upon CD200R pathway modulation.

Purpose of the Study:

  • To investigate the role of CD200 receptor (CD200R) activation in syngeneic mouse tumor models.
  • To determine the impact of agonistic anti-CD200R antibodies and CD200 deficiency on tumor development.

Main Methods:

  • Utilized syngeneic mouse models for melanoma.
  • Administered agonistic anti-CD200R antibodies (two clones).
  • Assessed tumor growth, burden, and immune cell infiltration in CD200-deficient mice and in the presence of CD200.

Main Results:

  • Agonistic anti-CD200R antibodies reached tumors but did not significantly impact tumor growth or myeloid cell infiltration.
  • CD200 deficiency led to decreased melanoma tumor burden.
  • Restoration of CD200 (endogenous or tumor-expressed) re-established melanoma growth.

Conclusions:

  • Blockade of the endogenous ligand CD200 inhibits tumor growth by preventing the tumorigenic effects of CD200R-expressing myeloid cells.
  • Agonistic anti-CD200R therapy showed no significant effect on tumor development in these models.
  • Targeting the CD200 ligand may be a more effective strategy than CD200R activation for cancer immunotherapy.

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