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Selective depletion of virus-specific CD8 T cells from the liver after PD-1 therapy with Fc-intact antibody during chronic infection - PubMed

5 hours ago
  • #FcγR interaction
  • #PD-1 immunotherapy
  • #CD8 T cell depletion
  • Mouse anti-mouse PD-1 antibodies with an intact Fc region selectively deplete PD-1+ virus-specific CD8 T cells in the liver during chronic infection.
  • This depletion is mediated by activating FcγR III on phagocytic cells, not natural killer cells, leading to increased viral titers and reduced tumor control in models.
  • Mutating the Fc region to block FcγR interaction prevents CD8 T cell depletion, resulting in effective immunotherapy.
  • Fc-intact anti-PD-1 antibodies may have negative effects in liver cancer, liver metastases, and chronic hepatotropic infections, but could benefit agonistic antibodies in autoimmunity.
  • The findings emphasize the critical role of the antibody Fc region in tailoring PD-1 therapies for different clinical applications.