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Updated: Apr 27, 2026
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Antimetastatic effects of blocking PD-1 and the adenosine A2A receptor
Deepak Mittal1, Arabella Young1, Kimberley Stannard2
1Authors' Affiliations: Immunology in Cancer and Infection Laboratory and Cancer Immunoregulation and Immunotherapy Laboratories, QIMR Berghofer Medical Research Institute, Herston; School of Medicine, University of Queensland, Queensland, Australia; and.
Abstract:
Adenosine targeting is an attractive new approach to cancer treatment, but no clinical study has yet examined adenosine inhibition in oncology despite the safe clinical profile of adenosine A2A receptor inhibitors (A2ARi) in Parkinson disease. Metastasis is the main cause of cancer-related deaths worldwide, and therefore we have studied experimental and spontaneous mouse models of melanoma and breast cancer metastasis to demonstrate the efficacy and mechanism of a combination of A2ARi in combination with anti-PD-1 monoclonal antibody (mAb). This combination significantly reduces metastatic burden and prolongs the life of mice compared with either monotherapy alone. Importantly, the combination was only effective when the tumor expressed high levels of CD73, suggesting a tumor biomarker that at a minimum could be used to stratify patients that might receive this combination. The mechanism of the combination therapy was critically dependent on NK cells and IFNγ, and to a lesser extent, CD8(+) T cells and the effector molecule, perforin. Overall, these results provide a strong rationale to use A2ARi with anti-PD-1 mAb for the treatment of minimal residual and metastatic disease.
Insights
Combining adenosine A2A receptor inhibitors (A2ARi) with anti-PD-1 antibodies effectively reduces cancer metastasis in mice. This novel cancer treatment strategy shows promise, particularly in tumors expressing high CD73 levels.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Metastasis Research
Background:
- Adenosine receptor antagonism presents a novel strategy for cancer treatment.
- Adenosine A2A receptor inhibitors (A2ARi) have a safe clinical profile in Parkinson disease.
- Metastasis is a primary driver of cancer-related mortality.
Purpose of the Study:
- To investigate the efficacy and mechanism of combining A2ARi with anti-PD-1 monoclonal antibody (mAb) in preclinical cancer metastasis models.
- To identify potential biomarkers for stratifying patients for this combination therapy.
Main Methods:
- Utilized experimental and spontaneous mouse models of melanoma and breast cancer metastasis.
- Administered combination therapy of A2ARi and anti-PD-1 mAb.
- Assessed metastatic burden, survival rates, and immune cell involvement (NK cells, CD8(+) T cells, IFNγ, perforin).
- Correlated treatment efficacy with CD73 expression levels in tumors.
Main Results:
- The combination of A2ARi and anti-PD-1 mAb significantly reduced metastatic burden and prolonged survival in mice compared to monotherapy.
- Treatment efficacy was dependent on high CD73 expression in tumors, suggesting its role as a predictive biomarker.
- The mechanism of action involved Natural Killer (NK) cells and Interferon-gamma (IFNγ), with a lesser contribution from CD8(+) T cells and perforin.
Conclusions:
- Combination therapy of A2ARi and anti-PD-1 mAb demonstrates significant potential for treating minimal residual and metastatic disease.
- CD73 can serve as a biomarker to identify patients likely to benefit from this combination immunotherapy.
- The study highlights the critical role of NK cells and IFNγ in mediating the anti-metastatic effects of this combined approach.
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