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Nivolumab receptor occupancy on effector regulatory T cells predicts clinical benefit

Masahiro Hosonuma1,2,3,4, Yuya Hirasawa4, Atsuo Kuramasu1

  • 1Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Setagaya-Ku, Japan.

Cancer Science
|January 23, 2024
PubMed

Insights

Nivolumab

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Immune checkpoint inhibitors (ICIs) like nivolumab have transformed cancer therapy, but response rates for solid tumors remain low (~10%-30%).
  • Predictors for patient prognosis and immune-related adverse events (irAEs) are crucial for optimizing ICI treatment.
  • Programmed cell death protein 1 (PD-1) receptor occupancy (RO) by PD-1 inhibitors may correlate with efficacy and irAEs, but requires characterization across T-cell subsets.

Purpose of the Study:

  • To investigate the association between nivolumab RO in distinct T-cell populations and patient prognosis.
  • To explore the relationship between nivolumab RO and the development of irAEs in cancer patients.
  • To determine the prognostic relevance of PD-1 RO on specific T-cell subsets in nivolumab-treated patients.

Main Methods:

  • Analysis of nivolumab receptor occupancy (RO) across different T-cell populations in 32 cancer patients.
  • Correlation of PD-1 RO levels with clinical benefits and overall survival.
  • Assessment of nivolumab RO in relation to the incidence of immune-related adverse events (irAEs).

Main Results:

  • Nivolumab RO on effector regulatory T cells (eTregs) was significantly lower in patients who achieved clinical benefits.
  • A significant negative association was found between PD-1 occupancy on eTregs and all-cause mortality.
  • No specific mention of irAE development in relation to RO in the abstract.

Conclusions:

  • Nivolumab RO on eTregs may serve as a prognostic biomarker for PD-1 inhibitor therapy.
  • Inhibition of PD-1/PD-ligand 1 (PD-L1) signaling on eTregs might potentially reduce anti-tumor effects.
  • Further research is warranted to validate eTreg PD-1 RO as a prognostic indicator in ICI treatment.
Keywords:
PD-1/PD-L1 signalingeffector regulatory T cellsimmune checkpoint inhibitornivolumabreceptor occupancy

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