New initiative aims to increase collaboration and accelerate high-impact cancer immunotherapy

The accelerated advancement of cancer immunology and immunotherapy, a type of biological therapy that boosts the immune system's ability to recognize and kill cancer cells, has significantly improved the effectiveness of cancer treatment and patient outcomes. One initiative is bringing together investigators who study immunotherapy to increase collaboration and accelerate high-impact immunotherapy research: the Cancer Immunology and Immunotherapy Initiative (CII) at the Robert H.Lurie Comprehensive Cancer Center of Northwestern University.

Together, Jeffrey Sosman, MD, professor of Medicine in the Division of Hematology and Oncology, and Bin Zhang, MD, PhD, professor of Medicine in the Division of Hematology and Oncology and of Microbiology-Immunology, lead the CII. The initiative, established in June 2020, aims to improve the understanding of the underlying mechanisms of cancer immunology and immunotherapy response, resistance and toxicity.

Since the discovery of immune checkpoint inhibitors in the 1990s, the field of cancer immunology has been advancing rapidly and improving the treatment of solid tumors entirely. Immune checkpoints keep the body’s immune system “in check”, ultimately preventing it from becoming too strong and accidentally destroying healthy cells.

These immune checkpoints are recruited into immune activation when immune checkpoint proteins, which are located on the surface of T-cells, engage with similar proteins on other cells such as cancer cells. When these proteins bind, they signal T-cells to turn off completely, preventing the immune system from destroying the cancer cell. Immune checkpoint inhibitors, however, prevent these proteins from binding together and allow T-cells to destroy cancer cells.

Over the last 15 years, immune checkpoint inhibitors and other types of immunotherapies have become the main line of defense against more than 10 different types of solid tumor cancers, including breast cancer, skin cancer, bladder cancer and hematologic malignancies.

I think immunologic approaches have become even more important than chemotherapy for many cancers. It’s been a complete transformation of oncology care.”

Jeffrey Sosman, MD, Professor of Medicine, Division of Hematology and Oncology

The cancer immunology and immunotherapy initiative

The CII provides resources and programs that foster collaboration among basic scientists and clinical investigators across the Lurie Cancer Center and Feinberg who are studying and treating the immune regulation of cancer.

“The overarching goal of the initiative is to integrate the resources and facilities across the center in cancer immunotherapy and help translate benchwork science findings into clinical applications,” Zhang said.

Currently, the CII supports investigators pursuing the following research topics: targeting immune suppression in the tumor microenvironment, nanotechnology and biomolecular engineering immunotherapy for cancer treatment, immune-related adverse events in cancer immunotherapy and immune profiling. They are also supporting new strategies that combine epigenetic modulation and immune checkpoint blockade in brain tumors, prostate tumors, skin cancers, renal carcinomas, bladder cancers, pancreatic cancers and ovarian cancers.

According to Sosman and Zhang, the overarching goal of the CII is to increase collaboration, excel high-impact immunotherapy research at the cancer center and help increase visibility and extramural funding for ongoing and future research projects.

“It’s great to have everybody interested in studying cancer immunology together pursuing a common goal. It’s also important for people who come at this research from different directions to be able to communicate their skills and try to drive more collaboration,” Sosman said.

Currently, the CII hosts monthly presentations and meetings for investigators to learn about and discuss research interests and seek collaborative opportunities, as well as workshops and roundtables, research progress meetings and a cancer immunology journal club.

The CII’s Immunotherapy Assessment Core also supports investigators by providing cutting-edge, high-throughput technologies and expertise for clinical and translational studies that aim to identify the mechanisms of immunopathogenesis at the single-cell level. The core is also equipped to support investigators who are exploring novel disease-specific biomarkers that may improve personalized immunotherapy approaches.

“That’s going to really guide us in how we stratify which patient populations will respond to more intensive therapy, different combinations of therapy or even less intensive therapy,” said Zhang, who co-directs the core with Isabelle C Le Poole, PhD, professor of Dermatology and Microbiology-Immunology.

As for the CII, Sosman and Zhang said their hope is for the initiative to eventually become a home for cancer immunotherapy investigators at the Lurie Cancer Center and across Northwestern.

“We’d like to see cancer immunology become a strong enough effort that it can become a major program within the cancer center and provide us a high profile in that area,” Sosman said.

Feinberg investigates cancer immunology

Recently, Feinberg investigators have made the following discoveries that have significantly reshaped the understanding of cancer immunology and immunotherapy:

• A team led by Amy Heimberger, MD, the Jean Malnati Miller Professor of Brain Tumor Research, recently discovered differences in the distribution and interaction of T-cells within the microenvironment of different regions of both brain tumors and brain metastases, according to findings published in the journal JCI Insight. The findings demonstrate how the immune cell interactome is distinct between cancer lineages.
• Northwestern Medicine scientists led by Adam Sonabend, MD, associate professor of Neurological Surgery, discovered a new biomarker to identify which patients with glioblastomas, the most common and malignant of primary brain tumors, might benefit from immunotherapy, with their findings published in Nature Cancer.
• Research led by Daniela Matei, MD, the Diana, Princess of Wales Professor of Cancer Research, chief of Reproductive Science in Medicine in the Department of Obstetrics and Gynecology, was senior author of the study published the Journal of Clinical Investigation, which found the protein FOXK2 promotes survival of cancer stem cells in ovarian cancer and that blocking this protein could reduce cancer recurrence after initial treatment.
• Investigators led by Dong-Hyun Kim, PhD, associate professor of Radiology in the Division of Basic and Translational Radiology Research, found that boosting function of natural killer cells with magnetic nanoparticles could make cancer immunotherapy more efficient, according to a Northwestern Medicine study published in ACS Nano. This method could unlock the potential to use natural killer cells on a variety of solid tumors.
• Maha Hussain, MBChB, the Genevieve E. Teuton Professor of Medicine in the Division of Hematology and Oncology, was co- author of the clinical trial published in Nature which used circulating tumor DNA to identify patients at risk of urothelial cancer relapse after surgical resection. The findings could help improve post- surgery treatment and demonstrate the power of personalized medicine in cancer.
• Research led by Chyung-Ru Wang, PhD, professor of Microbiology- Immunology, found that boosting mitochondrial function in a subpopulation of T-cells could make cancer immunotherapy more effective, according to findings published in the Proceedings of the National Academy of the Sciences. Specifically, Wang’s team found that CD1d-restricted natural killer T-cells are much more reliant on mitochondrial metabolism during development when compared with conventional CD4+ T cells, making them an attractive target for boosting immune function in cancer.
• Jaehyuk Choi, MD, PhD, the Jack W. Graffin Professor, discovered that an especially deadly subtype of T-cell lymphoma is distinguished by unique mutations in a specific protein signaling pathway, according to findings published in the journal Blood. Correcting the downstream effect of these mutations with a pharmacological inhibitor could be a promising precision medicine.