Johns hopkins Launches Public Atlas to Decode Pancreatic Cancer Immunotherapy Responses
A new, freely accessible resource promises to accelerate research into effective immunotherapies for one of the deadliest cancers.
Pancreatic cancer, a notoriously tough disease to treat, is the focus of a groundbreaking new initiative from Johns Hopkins Kimmel Cancer Center. Researchers have unveiled a extensive, web-based atlas of mass cytometry profiles, offering an unprecedented level of detail into the immune system’s response to various cancer therapies. This resource aims to clarify which treatments are driving specific immune reactions, ultimately paving the way for more personalized and effective treatment strategies.
Unlocking the Complexity of Immunotherapy
While immunotherapies – treatments that harness the body’s own immune system to fight cancer – have shown promise in some patients with pancreatic cancer, the results are often inconsistent. “Oncologists have achieved some immune system responses…but it’s not always clear which therapy is inducing what type of response,” according to the research team. To address this challenge, the Johns Hopkins investigators created a publicly available platform containing data from 260 cytometry profiles, representing immune cell markers from blood samples of 64 patients.
The atlas encompasses data from three clinical trials evaluating different combinations of pancreatic cancer vaccines and immune checkpoint inhibitors. “We have a platform for immune profiling based on 40-plus protein level markers to understand immune system responses,” explained a senior researcher. The team also tracked patients’ immune responses before and after treatment,allowing researchers to assess potential to predict treatment response.”What we’re hoping is that scientists can go to this repository, explore the data and generate hypotheses to carry out new studies,” a researcher noted.
Further data from the studies, including raw protein expression data, are available on zenodo, and analysis code can be found on GitHub.
A concurrent phase II study, also published in Cancer Immunology Research, investigated a treatment regimen for 57 patients with metastatic pancreatic cancer whose disease had progressed despite chemotherapy. The trial evaluated a combination of the vaccine CRS-207, the immunotherapies nivolumab and ipilimumab, with or without the vaccine GVAX. While overall response rates weren’t considerably different between the groups, detailed immunological analysis revealed that the vaccine-based approaches stimulated T-cell clones targeting the antigens mesothelin and KRAS, and these clones infiltrated the tumors.
These findings suggest that adding anti-CTLA4 to existing immunotherapy regimens could enhance the infiltration of antigen-experienced T cells, potentially becoming a crucial component of future immunotherapy strategies. “Adding anti-CTLA4 to the immunotherapy backbone significantly increases the infiltration of antigen-experienced T cells and is going to be an important part of future immunotherapy backbones,” a senior official stated.
The atlas study involved a large collaborative team including Dimitrios N. Sidiropoulos, Zhehao Zhang, Jennifer N. Durham, Soren Charmsaz, Nicole E. Gross, Jae W. Lee, Yanyi Sun, Susheel Perikala, Joseph A. Tandurella, dmitrijs Lvovs, Arik Mitschang, Gerard lemson, Sarah M. Shin, Alexei G. Hernandez, Sarah Mitchell, James M. Leatherman, Ludmila Danilova, Hao Wang, Elana J. Fertig, Elizabeth M. Jaffee, katherine M.Bever and Dung T. Le of Johns Hopkins.
The research was supported by grants from the Lustgarten Foundation for Pancreatic Cancer Research, the National Institutes of Health, the National Cancer Institute, SU2C/AACR, the Emerson Cancer Research Fund, an Allegheny Health Network grant, the JHU Revelation Award, and SPORE GI. this collaborative effort represents a significant step forward in the fight against pancreatic cancer, offering a powerful new tool for researchers seeking to unlock the full potential of immunotherapy.
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