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Unraveling the Complexity of the Tumor Microenvironment: New Study Lays Groundwork to Improve Success of Cancer Vaccines
Therapeutic vaccines are a promising and innovative approach to cancer therapy. To improve and accelerate their development, experts agree that it is necessary to better understand tumor microenvironments – the neighborhoods around tumors that can either help or hinder tumor growth and spread. A new study supported by Oncode Accelerator identified features of the tumor microenvironment associated with cancer vaccine success, paving the way for improved therapies for future patients.
The implementation of immunotherapies, such as immune checkpoint inhibitors, into clinical practice has transformed cancer care and brought new hope for patients. In recent years, therapeutic cancer vaccines – an innovative approach to cancer immunotherapy – have re-emerged as a promising approach to further increase response rates and survival for cancer patients.
Therapeutic cancer vaccines work by stimulating the patient’s immune system to recognize their tumor and control its growth. Ideally, these cancer vaccines both directly destroy tumor cells and establish an anti-tumor immune memory to protect patients over the long term. To realize the promise of therapeutic vaccines and accelerate their development, experts agree that it’s important to deepen our understanding of the tumor microenvironment (TME): the complex and dynamic ecosystem around tumors known to influence patient responses to immunotherapies – sometimes for the better, and sometimes for the worse.
Excitingly, a publication from the research group of Professor Sjoerd van der Burg of Leiden University Medical Center and the Oncode Institute has shed new light on the complexity of the TME. The publication, which was supported by Oncode Accelerator, used cutting edge techniques to better understand the TME and its relation to patient responses to a therapeutic cancer vaccine.
Understanding cancer vaccine success
The researchers focused on patients with vulvar high-grade squamous intraepithelial lesions (vHSIL), a tumor in development caused by human papillomavirus. For the study, they used tissues contributed by twenty different women who had received a therapeutic cancer vaccine after their diagnosis, highlighting the important role of patient contributions to preclinical research.
At the start of the study, the researchers already knew how well the therapeutic cancer vaccine had worked for the different patients: some had responded very well, some had partially responded, and others had not responded at all. The question was: why had the therapeutic vaccine worked better for some patients than others?
Digitally reconstructing the tumor microenvironment
Using a CosMx Spatial Molecular Imager, a machine that supports a cutting-edge method called single cell spatial transcriptomics, the researchers investigated whether specific hallmarks of the cells in the TME could be associated with the patients’ responses to the cancer vaccine. Using the CosMX data, the researchers were able to digitally reconstruct the patient-derived tissues into detailed 2D images that could be used to better understand the TME.
Ziena Abdulrahman, PhD student, Leiden University Medical Center, First author of the publicaionThe efficacy of immunotherapy is driven by the tumor microenvironment’s cellular composition and their spatial architecture — vHSIL complete responders to immunotherapeutic vaccination exhibit organized spatial immune ecosystems, underscoring the importance of spatial biology in both understanding anti-tumor immunity as well as for the advancement of therapeutic strategies
The resulting digital images of the tissue helped the researchers identify not only each type of cell in the tissue, but also the different functions of the cells present. Combining the data about the patients’ responses to the therapeutic vaccine onto the detailed digital map of cells, it was also possible to correlate the differences in the types, function and interactions of the immune cells infiltrating the patients’ tumors with clinical outcome.
By understanding the TME dynamics associated with a good response to therapeutic cancer vaccines, it may at first be possible to select the right patients and in a later stage even to create those conditions for future patients, to improve treatment efficacy. This study is an exciting example of how new and innovative research approaches can shed new light on why cancer therapies sometimes work better for some patients than others – with the ultimate goal to develop better and more personalized medicines for patients.
Accelerating the development of therapeutic cancer vaccines
To build on the findings of this study, a CosMx Spatial Molecular Imager has been purchased with Oncode Accelerator funding and is now operational at the Leiden University Medical Center. Through the Oncode Accelerator ecosystem, the Therapeutic Vaccines Workstream will continue to use valuable patient-derived materials and data to unravel the complexities of cancer and transform those findings into improved therapies for patients of all ages.
Sjoerd van der Burg, Professor at Leiden University Medical Center, Oncode InstituteThe development of therapeutic vaccines from concept to clinic is time-intensive, expensive, and requires different expertise at different stages. The Therapeutic Vaccines Workstream at Oncode Accelerator is uniquely suited to support accelerated development, offering an integrated and innovative, end-to-end infrastructure to support development from early R&D to later-stage GMP production
Would you like to find out more about how you can collaborate with the Therapeutic Vaccines Workstream, to leverage cutting-edge technologies and expertise to overcome the challenges of cancer vaccine development?
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About Leiden University Medical Center (LUMC)
At LUMC we work together to improve healthcare and people's health. This is what drives us. Every single day. From delivering care to providing care for health. In this process, we join forces to ensure that our initiatives come fully to fruition. As a public institution and innovator, we stand for the improvement of health care. We build towards prevention programs and optimal and innovative care through groundbreaking research and innovative education, together with our partners in the region and beyond. In doing so, we embrace the principles of value-driven care and the use of smart advanced technology. The engine for progress is the daily efforts and great commitment of our employees who work from our core values of personal, connecting, enquiring and curious.