Nav: Home

T cell revival correlates with lung cancer response to PD-1 immunotherapy

April 24, 2017

In lung cancer patients who were taking immunotherapy drugs targeting the PD-1 pathway, testing for CD8 T cell activation in their blood partially predicted whether their tumors would shrink. The results are scheduled for publication in PNAS.

Drugs targeting PD-1 or its ligand PD-L1 re-activate "exhausted" CD8 T cells by promoting their expansion and unleashing their ability to destroy cancer cells. Researchers at Emory Vaccine Center, led by co-senior author Rafi Ahmed, PhD, have been intensively studying the cells that are revived after inhibitory signals from PD-1 are blocked. Ahmed is director of the Vaccine Center and a Georgia Research Alliance Eminent Scholar.

Winship Cancer Institute investigators Rathi Pillai, MD and Suresh Ramalingam, MD, Winship's deputy director, teamed up with Alice Kamphorst, PhD and Ahmed's group to examine blood samples from 29 advanced non-small cell lung cancer patients undergoing immunotherapy treatment.

The patients were being treated at Winship Cancer Institute of Emory University with drugs blocking the PD-1 pathway, known as checkpoint inhibitors (nivolumab, pembrolizumab or atezolizumab). Blood samples were obtained before starting treatment and before each new treatment cycle, which lasted two to three weeks.

Most patients (70 percent) displayed an increase in the number of proliferating CD8 T cells in their blood after starting PD-1 targeted treatment -- an observable effect on the immune system. However, not all patients with an immunological response experienced a "partial clinical response", meaning that their tumors shrank by at least 30 percent. All patients with partial responses survived at least one year, while just one out of seven patients with progressive disease was reported to survive one year. Survival times for three patients were not available.

An early increase in activated PD-1+ CD8 T cells appears important. 80 percent of patients with clinical benefit exhibited PD-1+ CD8 T cell responses within 4 weeks of treatment initiation. In contrast, 70 percent of patients with disease progression had either delayed or absent PD-1+ CD8 T cell responses.

"We hypothesize that re-activated CD8 T cells first proliferate in the lymph nodes, then transition through the blood and migrate to the inflamed tissue," Ahmed says. "We believe some of the activated T cells in patients' blood may be on their way to the tumor."

Proliferating CD8 T cells displayed high levels of PD-1, as well as other molecules that influence their activity, which may be targets for combination therapies. The Emory/Winship team recently published a paper in Science, incorporating data from this study, showing that the costimulatory molecule CD28 is required for proliferation following PD-1-targeted treatment.

The current study supports a straightforward idea: if CD8 T cells appear to respond to immunotherapy, that's a good sign.

"Our ability to detect proliferating T cells in the blood and correlate this with clinical benefit is exciting since this captures a real-time assessment of the immune system's response to PD-1 directed therapies and is a readily accessible test from our patients' perspective," Pillai says.

While looking for activated T cells in the blood is not yet predictive enough for routine clinical use, such tests could provide timely information, says co-senior author Ramalingam. Monitoring the immune response could potentially help oncologists and patients decide, within just a few weeks of starting immunotherapy drugs, whether to continue with current treatment or combine it with something else.

"We are already doing larger studies to confirm these observations and extend them to other cancers beyond lung cancer," he says.
-end-
This work was funded in part by the National Institutes of Health and the T. J. Martell Foundation.

Emory Health Sciences

Related Lung Cancer Articles:

Lung cancer therapy may improve outcomes of metastatic brain cancer
A medication commonly used to treat non-small cell lung cancer that has spread, or metastasized, may have benefits for patients with metastatic brain cancers, suggests a new review and analysis led by researchers at St.
Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Lung transplant patients face elevated lung cancer risk
In an American Journal of Transplantation study, lung cancer risk was increased after lung transplantation, especially in the native (non-transplanted) lung of single lung transplant recipients.
Proposed cancer treatment may boost lung cancer stem cells, study warns
Epigenetic therapies -- targeting enzymes that alter what genes are turned on or off in a cell -- are of growing interest in the cancer field as a way of making a cancer less aggressive or less malignant.
Are you at risk for lung cancer?
This question isn't only for people who've smoked a lot.
Better equipped in the fight against lung cancer
Lung cancer is the third most common type of cancer in Germany and the disease affects both men and women.
New liquid biopsy-based cancer model reveals data on deadly lung cancer
Small cell lung cancer (SCLC) accounts for 14 percent of all lung cancers and is often rapidly resistant to chemotherapy resulting in poor clinical outcomes.
Cancer drug leads to 'drastic decrease' in HIV infection in lung cancer patient
Doctors in France have found the first evidence that a cancer drug may be able to eradicate HIV-infected cells in humans.
Air pollution is associated with cancer mortality beyond lung cancer
A large scale epidemiological study associates some air pollutants with kidney, bladder and colorectal cancer death.
More Lung Cancer News and Lung Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.