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Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity

Suzanne L Topalian1, Charles G Drake, Drew M Pardoll

  • 1Department of Surgery, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA. stopali1@jhmi.edu

Current Opinion in Immunology
|January 13, 2012
PubMed

Insights

Cancer cells present neoepitopes that the immune system can recognize. Targeting the Programmed Death-1 (PD-1) pathway with immune checkpoint blockade enhances anti-tumor immunity and shows promise for durable cancer control.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Genetic and epigenetic changes in cancer cells generate neoepitopes.
  • The immune system can recognize these neoepitopes.
  • Immune checkpoint blockade can enhance anti-tumor immunity.

Purpose of the Study:

  • To investigate the role of the Programmed Death-1 (PD-1) pathway in the tumor microenvironment.
  • To evaluate the potential of PD-1 pathway blockade as a cancer immunotherapy strategy.

Main Methods:

  • Preclinical models were used to study the PD-1 pathway.
  • Blocking agents targeting PD-1 pathway components were investigated.

Main Results:

  • The Programmed Death-1 (PD-1) pathway plays a critical role in creating an immunosuppressive tumor microenvironment.
  • Blocking agents targeting the PD-1 pathway demonstrated encouraging early clinical results.

Conclusions:

  • The PD-1 pathway is a validated and important target for cancer immunotherapy.
  • Immune checkpoint blockade targeting PD-1 can lead to durable tumor control by enhancing anti-tumor immunity.

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