Related Experiment Video
Updated: May 24, 2026
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
CD73-deficient mice are resistant to carcinogenesis
John Stagg1, Paul A Beavis, Upulie Divisekera
1Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. john.stagg@umontreal.ca
Abstract:
CD73 is a cell surface 5'-nucleotidase that converts AMP to adenosine, an immune suppressive molecule. CD73 may promote immune escape in cancer by contributing to the degradation of extracellular ATP released by dying cancer cells in hypoxic tumors or following chemotherapy. However, whether CD73 exerts a critical oncogenic function during tumorigenesis is unknown. In this study, we used genetically deficient mice to investigate its contribution to autochthonous tumor formation. CD73 deficiency suppressed the development of 3-methylcholanthrene (MCA)-induced fibrosarcomas through a mechanism relying upon IFN-γ, natural killer (NK) cells, and CD8(+) T cells. Similarly, CD73 deficiency also suppressed prostate tumorigenesis in TRAMP transgenic mice. Importantly, treatment with an anti-CD73 monoclonal antibody effectively suppressed growth of established MCA-induced tumors or TRAMP-C1 prostate tumors and inhibited the development of TRAMP-C1 lung metastases. The therapeutic activity of anti-CD73 monoclonal antibody against primary tumors was dependent on CD8(+) T cells, whereas its antimetastatic activity was dependent on host CD73 expression independent of T cells or NK cells. Taken together, our findings indicate that CD73 is a critical factor in tumorigenesis and that anti-CD73 antibodies may offer a novel generalized strategy to blunt immune escape and treat cancer.
Insights
CD73 promotes cancer immune escape and tumor growth. Inhibiting CD73 with antibodies suppressed tumor development and metastasis, offering a new cancer treatment strategy.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- CD73 (Cluster of Differentiation 73) is an enzyme converting AMP to adenosine, a molecule that suppresses immune responses.
- CD73 may facilitate cancer immune escape by degrading extracellular ATP, particularly in tumors.
- The precise role of CD73 in cancer development (tumorigenesis) remains unclear.
Purpose of the Study:
- To investigate the role of CD73 in the formation and progression of primary tumors.
- To evaluate the therapeutic potential of targeting CD73 in established cancers and metastasis.
- To elucidate the mechanisms underlying CD73's influence on anti-tumor immunity.
Main Methods:
- Utilized genetically modified mice lacking CD73 to study spontaneous tumor formation.
- Administered anti-CD73 monoclonal antibodies to mice with existing tumors and metastatic models.
- Assessed the impact of CD73 deficiency and antibody treatment on immune cell populations (IFN-γ, NK cells, CD8+ T cells) and tumor growth.
Main Results:
- CD73 deficiency significantly suppressed the development of fibrosarcomas and prostate tumors in mice.
- Anti-CD73 antibody treatment effectively inhibited the growth of established tumors and reduced lung metastasis.
- Therapeutic effects against primary tumors required CD8+ T cells, while anti-metastatic effects were independent of T cells and NK cells.
Conclusions:
- CD73 plays a critical role in promoting tumorigenesis and immune evasion.
- Targeting CD73 with monoclonal antibodies presents a promising therapeutic strategy for various cancers.
- Anti-CD73 antibodies demonstrate potential for both primary tumor treatment and preventing cancer spread.
Related Concept Videos
02:23Abnormal Proliferation
02:43Mouse Models of Cancer Study
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...