Pancreatic cancer remains one of the deadliest cancers, and progress in immunotherapy has been frustratingly slow. But what if we could unlock the secrets hidden within patient immune responses to these therapies? Researchers at Johns Hopkins Kimmel Cancer Center are offering a powerful new tool to do just that: a free, publicly accessible atlas of immunotherapy responses in pancreatic cancer. This resource promises to accelerate research and, ultimately, improve treatment outcomes for this devastating disease.
The Johns Hopkins team, supported in part by the National Institutes of Health, has unveiled a web-based atlas containing detailed mass cytometry profiles from patients with metastatic pancreatic cancer. Think of it as a comprehensive map of the immune landscape in these patients, charting how their immune systems react to various treatments. This atlas is available for anyone to use at sciserver.org/datasets/biomed/cytof_atlas.
Dr. Won Jin Ho, Associate Professor of Oncology at Johns Hopkins University School of Medicine and Associate Director of the Johns Hopkins Kimmel Cancer Center’s Convergence Institute, explains that the atlas compiles data from 260 cytometry profiles, reflecting the activity of immune cell markers, derived from blood samples of 64 patients participating in three clinical trials. These trials explored different combinations of two pancreatic cancer vaccines and two checkpoint inhibitor drugs. The goal? To decipher which therapies trigger specific immune responses. "We have a platform for immune profiling based on 40-plus protein level markers to understand immune system responses," Dr. Ho states. "We also study patients before and after treatment so that we can understand longitudinal responses, or how cancer treatments induce changes in the immune system."
The atlas, described in a January 12th publication in Cancer Immunology Research, isn't just a collection of raw data. It's a user-friendly resource with built-in tools that simplify comparisons of cell types and expression levels. This means researchers can easily analyze the information and generate new hypotheses for further investigation. The team plans to continuously update the atlas with new data, including information from tumor tissue analyses. The collaboration with the Institute for Data Intensive Engineering and Science at Johns Hopkins was crucial in developing the atlas's interface and tools.
Why is this atlas so important? Pancreatic cancer has a dismal five-year survival rate of only 13%, according to the Pancreatic Cancer Action Network. Dr. Ho emphasizes that this grim statistic motivated the team to make their findings publicly available. "Pancreatic cancer is such a lethal disease, which was our motivation to make this public," he says. While previous immunotherapy trials conducted by the group haven't always achieved the desired clinical outcomes, they have provided valuable insights into the complex interplay between the immune system and pancreatic cancer. This atlas builds on those insights, offering a foundation for future research.
Dr. Dimitrios Sidiropoulos, a computational cancer immunologist at Johns Hopkins, co-led the data integration across the trials. His work revealed distinct immune signatures in the blood associated with specific immunotherapies, signatures that can even be projected onto tumor tissues. This demonstrates the atlas's potential to guide the development of more effective therapies. "What we’re hoping is that scientists can go to this repository, explore the data and generate hypotheses to carry out new studies," says Dr. Ho.
Beyond the atlas itself, the researchers have also made raw protein expression data available on zenodo (doi.org/10.5281/zenodo.13937090) and analysis code on GitHub (github.com/wjhlab/Immunotherapy-Atlas), further enhancing its accessibility and utility.
But here's where it gets controversial... The same issue of Cancer Immunology Research features another study from Dr. Ho and colleagues, detailing the results of a phase II clinical trial involving 57 patients with metastatic pancreatic cancer whose disease had progressed despite chemotherapy. Led by Dr. Dung Le and Dr. Katie Bever, this trial randomized patients to receive either the vaccine CRS-207 plus the immunotherapies nivolumab (anti-PD1) and ipilimumab (anti-CTLA4), with or without the vaccine GVAX. While the response rates weren't significantly different between the two groups, in-depth immunologic studies, co-led by Dr. Amanda Huff, revealed that the vaccine-based regimens could generate T-cell clones specific to the antigen mesothelin and the mutation KRAS. Crucially, these clones were found to infiltrate the tumors. These findings highlight the potential of these vaccine-based regimens to elicit a targeted immune response within the tumor microenvironment.
Dr. Ho believes that adding anti-CTLA4 to the immunotherapy backbone is significant because it significantly increases the infiltration of antigen-experienced T cells and "is going to be an important part of future immunotherapy backbones."
The atlas study was a collaborative effort, with contributions from numerous researchers at Johns Hopkins. The work was supported by grants from various organizations, including the Lustgarten Foundation for Pancreatic Cancer Research and the National Institutes of Health.
It's important to note that Dr. Ho has disclosed potential conflicts of interest, including patent royalties and speaking/travel honoraria. Similarly, other researchers have reported financial relationships with various companies in the pharmaceutical and biotechnology industries. These relationships are managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.
This new atlas represents a significant step forward in the fight against pancreatic cancer. By providing researchers with a comprehensive resource for studying immunotherapy responses, it has the potential to accelerate the development of more effective treatments. What are your thoughts on the role of open-access data in accelerating cancer research? Do you believe that sharing data, even with potential conflicts of interest, ultimately benefits patients?
