Presidential Address: Using the immune system to fight melanoma
In this year’s Presidential Address, Fighting Melanoma with the Immune System, AACR President Antoni Ribas, MD, PhD, FAACR, discussed how researchers are working to change the treatment paradigm for patients with melanoma through next-generation techniques that stimulate immune response and amplify antitumor activity. He also reflected on his term as AACR President.
“We understand why there is antitumor activity with anti-PD-1 therapies. It is because there are pre-existing T cells that are trying to attack the tumor, and we know that they are trying because there are mutations in the tumor that can be targeted,” Ribas said. “You can find multiple T cell receptors that will recognize those mutations, but the interferon signaling was stopped because PDL-1 would turn off the T cells and there was not enough interferon to be able to mount an immune response.”
If the PD-1 pathway is blocked, he said, interferon signaling proceeds and the cancer cell actually becomes an enabler of the antitumor immune response and amplifies the response through interferon and signaling the production of interferon response genes.
“If this doesn’t happen naturally, we can try to induce it by artificial triggering of interferon pathway signaling through pattern recognition receptors, or by taking the T cell receptors from patients who do not respond and take those rare T cell receptors and engineer them into more T cells and give them back to patients,” Ribas said. “As we do this, we can do next-generation editing so we can further empower those T cells.”
In closing his address, Ribas said he was grateful for the honor of serving as AACR President and acknowledged the challenges that everyone has faced over the past year. Among the work he is most proud of, he said, is the establishment last spring of the COVID-19 and Cancer Task Force.
“There has been a lot that cancer researchers have done to help in the pandemic by studying immune responses to the virus and by studying what happens in tumors,” Ribas said. “The platforms for sequencing and for antibody detections to the virus and the use of platforms for cancer vaccines quickly allowed the development of the first COVID-19 vaccines that will allow us to go back to normal life.”
Beyond the pandemic, Ribas said he was also proud of the AACR and the entire cancer research community for its response to ongoing calls for an end to social and racial injustices.
“When it was time to call out things that were happening, things that were really troubling us, the AACR was there for us. As racial injustices continued in our society that were negatively impacting many of our colleagues that work in cancer research and drug development, we convened panels to address that,” he said. “The landmark release of the AACR Cancer Disparities Progress Report 2020 shows how AACR has been studying the root causes for prevalent injustices that impact so negatively on all of the fields.”
Finally, Ribas thanked the AACR Board of Directors, AACR staff, and everyone who volunteered and served on committees for their hard work and dedication over the past year.
“Thanks to their work, the AACR will emerge from this pandemic even stronger, and with more programs and more things that will benefit the quest for advancing cancer treatments for all,” he said.
Registrants can watch a replay of the address through June 21, 2021.