From "Hellstrom Paradox" to anti-adenosinergic cancer immunotherapy.

Purinergic Signalling
Dmitriy LukashevAkio Ohta

Abstract

Cancer therapy by endogenous or adoptively transferred anti-tumor T cells is considered complementary to conventional cancer treatment by surgery, radiotherapy or chemotherapy. However, the scope of promising immunotherapeutic protocols is currently limited because tumors can create a "hostile" immunosuppressive microenvironment that prevents their destruction by anti-tumor T cells. There is a possibility to develop better and more effective immunotherapies by inactivating mechanisms that inhibit anti-tumor T cells in the tumor microenvironment and thereby protect cancerous tissues from immune damage. This may be now possible because of the recent demonstration that genetic deletion of immunosuppressive A2A and A2B adenosine receptors (A2AR and A2BR) or their pharmacological inactivation can prevent the inhibition of anti-tumor T cells by the hypoxic tumor microenvironment and as a result facilitate full tumor rejection [Ohta A, Gorelik E, Prasad SJ et al (2006) Proc Natl Acad Sci USA 103(35):13132-13137]. This approach is based on in vivo genetic evidence that A2AR play a critical role in the protection of normal tissues from overactive immune cells in acutely inflamed and hypoxic areas. The observations of much improved T-cel...Continue Reading

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Jun 26, 2013·Purinergic Signalling·Geoffrey Burnstock, Francesco Di Virgilio
Apr 12, 2011·Immunologic Research·Ioannis DrygiannakisIan J Glomski
Jun 24, 2009·Nature Reviews. Clinical Oncology·Swethajit Biswas, Tim Eisen
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