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Wistar Science Highlights: New Research in Melanoma and Cancer Immunotherapy

Two Wistar studies published in the past month described the creation of a comprehensive collection of pre-clinical models for melanoma research and the identification of novel aspects of the tumor-immune cell crosstalk that affects the response to immunotherapy. In addition, a Wistar paper was recommended by the F1000 initiative.

Meenhard Herlyn, D.V.M., D.Sc., Caspar Wistar Professor in Melanoma Research, director of Wistar’s Melanoma Research Center and professor in the Molecular and Cellular Oncogenesis Program, and his team have created a comprehensive collection of patient-derived xenografts (PDXs) for pre-clinical modeling of melanoma.

PDXs are cancer models created by transplanting a patient’s primary tumor directly into an immunodeficient mouse. They provide a source of tumor tissue that is significantly more representative of the clinical lesion than tumor cells grown in a petri dish. PDXs can be used to develop personalized treatments and evaluate responses to different types of therapy.

“In order to keep up with the development of new treatment strategies, we need improved models that reflect the complex landscape of melanoma,” said Herlyn. “We created a live tissue resource that represents the full spectrum of clinical, therapeutic, mutational and biological heterogeneity of the disease and will be a valuable tool available to the melanoma research community.”

New findings from the lab of Dmitry I. Gabrilovich, M.D., Ph.D., Christopher M. Davis Professor and program leader of the Immunology, Microenvironment and Metastasis Program, expanded our understanding of the ongoing conversation in the tumor microenvironment between the tumor itself and different types of surrounding cells, which talk to each other via the production of chemical messengers.

This intricate crosstalk helps explain the limited clinical success of a promising immunotherapy that targets an immune cell population called tumor-associated macrophages (TAMs). Because TAMs promote tumor cell proliferation and invasion and can inhibit the antitumor immune response, several recent studies have explored inhibition of the CSF-1 receptor (CSF-1R)—which mediates the functions and survival of TAMs — as a strategy to eliminate TAMs and reduce tumor growth.

Gabrilovich and colleagues found that this strategy, while effective at depleting TAMs from the tumor microenvironment, also resulted in the unexpected recruitment of another immunosuppressive population called polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), which favor tumor progression and mediate resistance to immunotherapy.

“Our findings suggest that in order to achieve a significant therapeutic effect, we need to reduce the presence of both immunosuppressive populations,” Gabrilovich said.

Ken-ichi Noma, Ph.D., associate professor in the Gene Expression and Regulation Program, had his most recent paper recommended in F1000Prime (Faculty of 1000) as being of special significance in its field. F1000Prime publishes recommendations of the most relevant articles in biology and medicine from a virtual “faculty” composed of more than 10,000 international experts.

Dr. Noma’s paper, published in last month’s Nature Structural & Molecular Biology, uncovered new aspects of the three-dimensional organization of the genome, specifically how the genetic material is compacted and de-compacted in a timely fashion during the different phases of the cell cycle.

F1000 provides an updated consensus map of important studies and scientific trends, highlighting the significance and relevance of Noma’s research.