MedicalResearch.com Interview with:
James S. Welsh, MS, MD, FACRO
President, American College of Radiation Oncology
Professor and Medical Director
Director of Clinical & Translational Research
Department of Radiation Oncology
Stritch School of Medicine Loyola University- Chicago
Cardinal Bernardin Cancer Center
Maywood, IL 60153
Chief of Radiation Oncology
Hines VA Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Welsh: Cancer immunotherapy could represent a truly powerful means of addressing cancer. Although immunotherapy itself is not new, there are new agents and combinations of older agents (including radiation therapy) that could prove more successful than anything we have seen in many years. The data in melanoma thus far is quite encouraging and this preliminary success could possibly extend to many other malignancies as well.
MedicalResearch.com: What should readers take away from your report?
Dr. Welsh: We are currently in a cancer immunotherapy renaissance. Although earlier generations of cancer immunotherapy met with little success, the present go-around is far more effective and exciting. This is largely thanks to a better – but still incomplete – understanding of the tumor microenvironment and how it subverts the immune system. Instead of attacking antigenic, highly-mutated, malignant cells, the immune system is “fooled” into protecting cancer cells. The latest generation of cancer immunotherapy is reversing the spell that the tumor microenvironment has cast on the immune system. This new ability to recognize its enemy is allowing the immune system to launch attacks that it previously was unable to mount. Even if powerful, the immune system was unable to effectively “see” the cancer cells it should be eliminating. The current generation of cancer immunotherapy is taking the blinders off the immune system and enabling it to so what it wants to do – eradicate unwanted cancer cells. Radiation therapy might be able to potentate the newly awakened immune system by acting as a “vaccine” to show the immune system what it should be on the lookout for. Radiation might also work by multiple other mechanisms such as altering the ratio of regulatory t-cells to effector t-cells.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Welsh: I believe there is reason to believe that there could be significant synergy between radiation therapy and immunotherapy. For this reason i would encourage research into questions such as:
- What is the best radiation dose and dose-rate to elicit an immune response?
- When is the best time to add radiation to immunotherapy? For instance, is it better to administer radiation before starting, during or after completion of checkpoint inhibitor therapy?
Although previous generations of cancer immunotherapy (such as interferons and interleukins) failed, part of the reason for this failure was our lack of understanding or appreciation of the “brakes” on the immune system. These agents strengthened the immune response but without taking the brakes off, we got nowhere. Now, with a better grasp of the inhibitory aspects of the tumor microenvironment and a better appreciation of immunological synapses and the “brakes” or checkpoints that are often present on t cells responses to cancer, it could be that integrating the older forms of immunotherapy with the new agents that take off the brakes could yield effective new combinations.
Of course, we will have to be wary of potentially severe autoimmune reactions.
Another often overlooked means of modulating the immune system is low dose/low dose-rate total body irradiation. I think this forgotten technique might be worth re-examining during this cancer immunotherapy renaissance.
MedicalResearch.com: Is there anything else you would like to add?
Dr. Welsh: I admit that i am biased but based on the reading and research that went into my book, “sharks get cancer, mole rat’s don’t: how animals could hold the key to unlocking cancer immunity in humans” i now firmly believe that cancer immunotherapy has a very bright future. With a better understanding of the highly immune-suppressing tumor microenvironment and how new agents might overcome this suppression, new combinations of old and new forms of cancer immunotherapy might be able to effectively turn the immune system loose on its ancient enemy and gain the upper hand at last.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Kyle Stang, Scott Silva, Alec M. Block, James S. Welsh. The integration of radiation therapy and immunotherapy in melanoma management. Journal of Radiation Oncology, 2016; DOI: 10.1007/s13566-016-0256-5
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