Cancer immunotherapy drugs blocking the PD-1 pathway – known as checkpoint inhibitors – are now FDA-approved for melanoma, lung cancer and several other types of cancer. These drugs are often described as “releasing the brakes” on dysfunctional T cells.
A new study from Emory Vaccine Center and Winship Cancer Institute researchers shows that even if the PD-1-imposed brakes are released, the tumor-specific T cells still need “fuel” to expand in numbers and restore effective immune responses. That fuel comes from co-stimulation through a molecule called CD28.
The results were published Thursday by the journal Science.
Despite the success of PD-1-targeting drugs, many patients’ tumors do not respond to them. The study’s findings indicate that CD28’s presence on T cells could be a clinical biomarker capable of predicting whether drugs targeting PD-1 will be effective. In addition, the requirement for CD28 suggests that co-stimulation may be missing for some patients, which could guide the design of combination therapies.
For the rest of our press release and quotes from authors Rafi Ahmed, Alice Kamphorst and Suresh Ramalingam, please go here. For some additional links and thoughts on PD-1 and CD28, read on:
Are you experienced? Your immune system undoubtedly is. Because of vaccinations and infections, we accumulate memory T cells, which embody the ability of the immune system to respond quickly and effectively to bacteria or viruses it has seen before.
Not so with mice kept in clean laboratory facilities. Emory scientists think this difference could help explain why many treatments for sepsis that work well in mice haven’t in human clinical trials.
Mandy Ford has teamed up with Craig Coopersmith to investigate sepsis, a relatively new field for her, and the collaboration has blossomed in several directions
“This is an issue we’ve been aware of in transplant immunology for a long time,” says Mandy Ford, scientific director of Emory Transplant Center. “Real life humans have more memory T cells than the mice that we usually study.”
Sepsis is like a storm moving through the immune system. Scientists studying sepsis think that it has a hyper-inflammatory phase, when the storm is coming through, and a period of impaired immune function afterwards. The ensuring paralysis leaves patients unable to fight off secondary infections.
In late-stage sepsis patients, dormant viruses that the immune system usually keeps under control, such as Epstein-Barr virus and cytomegalovirus, emerge from hiding. The situation looks a lot like that in kidney transplant patients, who are taking drugs to prevent immune rejection of their new organ, Ford says.
Ford’s team recently found that sepsis preferentially depletes some types of memory T cells in mice. Because T cells usually keep latent viruses in check, this may explain why the viruses are reactivated after sepsis, she says. Read more
Gina Kolata has a section front story in Tuesday’s New York Times exploring the potential of a relatively new class of anticancer drugs. The drugs break through “shields” built by cancers to ward off the threat posed by the patient’s immune system. Many are based on blocking PD-1, an immune regulatory molecule whose importance in chronic infections was first defined by Emory’s Rafi Ahmed.
Of course, not every cancer research developmentÂ describedÂ as transformative inÂ the New York TimesÂ lives up to the hype. But the clinical trial results, reportedÂ in the New England Journal of Medicine, are solid enough that the researchers Kolata talks with think they are seeing “a moment in medical history when everything changed.”Â [Winship Cancer Institute’s John Kauh was a co-author on one of the 2012 NEJM papers.]
Let’s take a moment to examine some of the roots of this story.Â Rafi Ahmed didnâ€™t set out to study cancer. For the last two decades, he and his colleagues have been studying T cells, parts of the immune system that are critical for responding to infections. Read more