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Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy

Maud Mayoux1, Andreas Roller2, Vesna Pulko1

  • 1Cancer Immunotherapy Discovery, Pharmaceutical Research and Early Development, Roche Innovation Center Zurich, Schlieren 8952, Switzerland.

Science Translational Medicine
|March 13, 2020
PubMed

Insights

PD-L1 blocking antibodies enhance cancer immunity by targeting dendritic cells (DCs), not just T cells. This approach re-engages DCs to boost T cell responses, improving survival in cancer patients.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Immunotherapy

Background:

  • Immune checkpoint inhibitors targeting the PD-L1/PD-1 axis are effective cancer treatments.
  • Understanding how these therapies activate anticancer immunity is crucial for broader patient benefit.

Purpose of the Study:

  • To investigate the role of dendritic cells (DCs) as a target for PD-L1 blocking antibodies.
  • To elucidate the mechanism by which PD-L1 blockade enhances anti-tumor T cell responses.

Main Methods:

  • Analysis of PD-L1 expression on peripheral and tumor-associated DCs in cancer patients.
  • Assessment of the impact of PD-L1 blockade on DC function and T cell priming in preclinical models.
  • Correlation of a DC gene signature with overall survival in patients treated with atezolizumab.

Main Results:

  • PD-L1 is highly expressed on DCs in cancer patients.
  • PD-L1 blockade releases B7.1 (CD80) on DCs, facilitating the B7.1/CD28 interaction and enhancing T cell priming.
  • A DC gene signature associated with PD-L1 blockade correlated with improved survival in renal cell carcinoma and non-small cell lung cancer patients.

Conclusions:

  • Dendritic cells are a key target of PD-L1 blocking antibodies.
  • PD-L1 blockade reinvigorates DC function, leading to enhanced anticancer T cell immunity.
  • Targeting DCs via PD-L1 blockade offers a promising strategy for improving cancer immunotherapy outcomes.

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