First (and massive) whole-genome study of IBD in African Americans

In African Americans, the genetic risk landscape for inflammatory bowel disease (IBD) is very different from that of people with European ancestry, according to results of the first whole-genome study of IBD in African Americans. The authors say that future clinical research on IBD needs to take ancestry into account. Findings of the multi-center study, which analyzed the whole genomes of more than 1,700 affected individuals with Crohn’s disease and ulcerative colitis and more than Read more

Emory researchers SNARE new Alzheimer’s targets

Diving deep into Alzheimer’s data sets, a recent Emory Brain Health Center paper in Nature Genetics spots several new potential therapeutic targets, only one of which had been previous linked to Alzheimer’s. The Emory analysis was highlighted by the Alzheimer’s site Alzforum, gathering several positive comments from other researchers. Thomas Wingo, MD Lead author Thomas Wingo and his team -- wife Aliza Wingo is first author – identified the targets by taking a new approach: tracing Read more

Greg Lesinski

Peeling away pancreatic cancers’ defenses

At Winship Cancer Institute, pancreatic cancer researcher Greg Lesinski and colleagues have a new paper in Molecular Cancer Therapeutics. It’s about a combination immunotherapy approach that gets through pancreatic cancers’ extra defenses, and it represents the preclinical counterpart to a clinical trial that is underway and almost finished at Winship, under the direction of GI oncologist Bassel El-Rayes.

Immunotherapies have transformed how other forms of cancer are treated, but for pancreatic cancers, an obstacle is getting through the dense layers of cellular shielding that the cancers build around themselves. Pancreatic cancers create “nests” of fibrotic stellate cells that pump out inflammatory cytokines such as IL-6.

Pancreatic cancer is anticipated to become the second deadliest cancer in the United States by 2030, surpassing breast and colon cancer. 

“Inflammation and a good immune response don’t always go hand in hand,” El-Rayes told us, for a 2018 Winship magazine article. “High IL-6 causes immune exhaustion, and keeps the good cells out of the tumor.”

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Posted on by Quinn Eastman in Cancer Leave a comment

Update on pancreatic cancer: images and clinical trial

In 2018, Winship magazine had a feature story on pancreatic cancer. Our team developed an illustration that we hoped could convey the tumors’ complex structure, which contributes to making them difficult to treat. Oncologist Bassel El-Rayes described how the tumors recruit other cells to form a protective shell.

“If you look at a tumor from the pancreas, you will see small nests of cells embedded in scar tissue,” he says. “The cancer uses this scar tissue as a shield, to its own advantage.”

With El-Rayes and fellow oncologist Walid Shaib, Greg Lesinski’s lab recently published a paper in JCI Insight. The point of the paper was to look at how chemotherapy changes immune activity in the tumor microenvironment, but we also get vivid images giving us a glimpse of those nests. It helps to view these images as large as possible, so please check them out at the journal’s site, which has no paywall.

Regions stained green are tumor-rich; red regions are immune cell-rich, and blue regions are rich in stromal cells (stellate/fibroblast cells). The goal is to get immune cells to envelop the tumors more, like in square 8.

The 2018 magazine story also laid out some of Lesinski’s and El-Rayes’ ideas.

Based on his lab’s recent success in animal models, Lesinski thinks that combining an immunotherapy drug with agents that stop IL-6 could pry open pancreatic cancers’ protective shells. In those experiments, the combination resulted in fewer stellate cells and more T cells in the tumors. Fortunately, a couple of “off-the-shelf” options, drugs approved for rheumatoid arthritis, already exist for targeting IL-6, Lesinski says.

On that theme, we noticed that a clinical trial was posted on clinicaltrials.gov in December that implements those proposals: “Siltuximab and Spartalizumab in Patients With Metastatic Pancreatic Cancer”. El-Rayes is the principal investigator, and it is not yet recruiting. Siltuximab is an antibody against IL-6 and spartalizumab is a second generation PD-1 inhibitor.

Update: The XL888 + pembrolizumab study mentioned in the article is also moving along, presented by Mehmet Akce at the Gastrointestinal Cancers Symposium.

Posted on by Quinn Eastman in Cancer Leave a comment