Publications

Our researchers work diligently to not only make clinical advancements, but also scientific discoveries that are frequently published in the top scientific journals such as Nature and Cancer Discovery. Listed here are a selection of the most relevant articles authored by PCRC researchers.

pcrc publication covers - see legends below for full details of each cover
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Feature Articles

Robert Vonderheide, Director of the Abramson Cancer Center and PCRC member, was featured in a video from Cancer Research Institute, a non-profit organization supporting cancer research. In the video, Dr. Vonderheide explains the critical role of private funding in advancing our mission. View the video here.

Work from the laboratories of Ben Stanger and Robert Vonderheide have studied new inhibitors of KRAS, the initiating genetic driver of most pancreatic cancers. Their studies reveal that KRAS inhibition reprograms the immune system, providing an immuno-stimulatory effect in addition to a direct anti-tumor effect:

Work from the laboratories of Katy Wellen and Celeste Simon has explored the metabolic vulnerabilities emerging from the nutrient- and oxygen-deprived tumor microenvironments associated with most pancreatic cancers:

Work from the laboratory of Gregory Beatty has revealed details about the tumor microenvironment in pancreatic cancer and novel opportunities for immunotherapy:

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Legends:

On the cover (Immunity): Tumors possess heterogeneous immune tumor microenvironments (TMEs), with some that are T-cell inflamed (hot) and others that are non-T-cell inflamed (cold). In this issue of Immunity, Li, Byrne et al. (178–193) generate an experimental system that recapitulates this heterogeneity in mouse models of pancreatic cancer. The authors find that tumor-intrinsic features determine the nature of the immune infiltrate and reveal a central role for the chemokine CXCL1 in the generation of a non-T-cell-inflamed tumor microenvironment. Cold tumors are depicted as blue water, wherein cancer cells (crab) recruit suppressive myeloid cells (yellow sea anemone) to protect against attack from T cells (octopus). In hot tumors (red water), cancer cells fail to recruit protective myeloid cells and are targeted by T cells following immunotherapy. Illustration by Cuncun Zhao.

On the cover (Developmental Cell): Tumor cells that have undergone epithelial-mesenchymal transition (EMT) and entered the circulation are represented by koi fish in a pond. Cells that undergo partial EMT (group of speckled fish) internalize their epithelial junctions (speckles) and disseminate by collective migration. In contrast, cells that undergo complete EMT (solitary fish) repress the epithelial program through transcriptional regulation and disseminate as single cells. For more on cancer cell migration modes, see Aiello et al. (pp.681–695) and the related paper from Reichert et al. (pp. 696–711).

On the cover (Cancer Cell): Fresh insights for exploiting the immune system's strengths and vulnerabilities are paving the way to a revolution in cancer treatment. Following FDA approvals of immune checkpoint antibodies and chimeric antigen receptor T cells, current research efforts now aim to understand the role of T cell priming and dysfunction in the tumor microenvironment as well as the influence of other immune regulatory factors, including the microbiome. Researchers are also investigating the effects of oncolytic viruses on anti-tumor immunity. The translation of these scientific advances to novel clinical trials is as rapid and as expansive as ever before, suggesting we have only seen the tip of the iceberg for cancer immunotherapy. For more details, see the four Perspective articles and one Review article in this issue. Artwork by Abby Ernst, Penn Medicine.

On the cover (Cancer Immunology Research): Patients respond better to immunotherapy if their tumors have generated abundant neopeptides. However, not all identified neopeptides are immunogenic, even after selection based on algorithms predicting affinity for class I or class II major histocompatibility antigens. By comparing the neopeptides from more than 6,300 patients with 27 types of tumors, Rech and colleagues identified alternatively defined neopeptides by their ability to bind to MHC at least 10 times better than their normal unmutated counterparts. These “ADNs” provide a rich, unexplored pool of possible antigenic targets for immunotherapy. Read more starting on page 276 of this issue. The original image of a Masson's trichrome stained pancreatic tumor was provided by Dr. Emma E. Furth, Professor of Pathology and Laboratory Medicine, Head of Gastrointestinal Pathology, Hospital of the University of Pennsylvania. Connective tissue, blue; cells, magenta. Artwork by Lewis Long.