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Publications

Parker Institute investigators evolve the field of immunotherapy with impactful discoveries.

 

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1,440

Research papers published
by our members

324

Journals

96

Multi-institutional papers

Statistics as of PICI’s launch in April 2016

Great science gets published.

Parker Institute investigators regularly publish their work in top-notch scientific journals. With each new discovery, our researchers take a step toward a solution for cancer. Here, we highlight a selection of novel papers that are impactful to both patients and the field of immunotherapy. These papers are led by PICI investigators and many are collaborations between our members across institutions. We will continue to add to this list so check back soon for new research.

Featured Publications

Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non–Small-Cell Lung Cancer

Kathryn C. Arbour, Laura Mezquita, Niamh Long, Hira Rizvi, Edouard Auclin, Andy Ni, Gala Martínez-Bernal, Roberto Ferrara, W. Victoria Lai, Lizza E.L. Hendriks, Joshua K. Sabari, Caroline Caramella, Andrew J. Plodkowski, Darragh Halpenny, Jamie E. Chaft, David Planchard, Gregory J. Riely, Benjamin Besse and Matthew D. Hellmann

Journal of Clinical Oncology, August 20, 2018
Summary of work

Corticosteroids are commonly used in late-stage non-small-cell lung cancer patients (NSCLC) who receive checkpoint inhibitors to control a variety of immune-related side effects such as shortness of breath or fatigue. However, there is evidence to indicate that corticosteroids could dampen the effectiveness of immunotherapy. To investigate further, Parker Institute researcher Matthew Hellmann, MD, reviewed records of 640 NSCLC patients treated with a single PD-1 or PD-L1 checkpoint inhibitor immunotherapy and found that corticosteroid use (of ≥ 10 mg of prednisone or a drug equivalent) was strongly associated with a poorer outcome in patients. The work was done in cross-collaboration between colleagues at Memorial Sloan Kettering Cancer Center and the Gustave Roussy Cancer Center.

Why this is impactful to patients

PICI research scientist Christine Spencer, PhD, explains, “this is the first paper to show that steroid use is indeed associated with poorer patient outcomes in the context of checkpoint immunotherapy.” It suggests that clinicians should be cautious and conservative with using steroids before and at the start of PD-1/PD-L1 treatment. In addition, more research needs to be done to study the effect of steroids on other common NSCLC treatments that combine chemotherapy and immunotherapy.

Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells

Bertram Bengsch, Takuya Ohtani, Omar Khan, Manu Setty, Sasikanth Manne, Shaun O’Brien, Pier Federico Gherardini, Ramin Sedaghat Herati, Alexander C. Huang, Kyong-Mi Chang, Evan W. Newell, Niels Bovenschen, Dana Pe’er, Steven M. Albelda, and E. John Wherry

Immunity, May 15, 2018
Summary of work

During cancer and chronic infections, T-cells that fight off disease can become exhausted, preventing the body from being able to control the disease effectively. In this paper, Parker Institute researchers at the University of Pennsylvania developed a method to better identify and characterize exhausted T-cells in cancer and HIV patients, using an approach that incorporates epigenetic and gene expression screens followed by mass cytometry. E. John Wherry, PhD, Parker Institute co-director at the University of Pennsylvania, is senior author and PICI project member Bertram Bengsch, PhD, is first author. Co-authors include Parker Bridge Scholar Alexander Huang, MD, PhD, and Pier Federico Gherardini, PhD, Parker Institute associate director of technology development.

Why this is impactful to patients

Understanding more about exhausted T-cells could prove helpful when creating new therapies that could aid cancer or HIV patients. “Interestingly, in this paper the scientists identify combinations of immunotherapy targets on exhausted T-cell populations that could lead to novel combinations of immuno-oncology drugs for testing in clinical trials,” said Nicholas Bayless, PhD, a Parker Institute research scientist on the informatics team.

Transcript-Indexed ATAC-seq for Precision Immune Profiling

Ansuman T. Satpathy, Naresha Saligrama, Jason D. Buenrostro, Yuning Wei, Beijing Wu, Adam J. Rubin, Jeffrey M. Granja, Caleb A. Lareau, Rui Li, Yanyan Qi, Kevin R. Parker, Maxwell R. Mumbach, William S. Serratelli, David G. Gennert, Alicia N. Schep, M. Ryan Corces, Michael S. Khodadoust, Youn H. Kim, Paul A. Khavari, William J. Greenleaf, Mark M. Davis and Howard Y. Chang

Nature Medicine, April 23, 2018
Summary of work

Only a small fraction of human T-cells recognize and destroy tumors. How do you separate the signals in these few T-cells from the rest? Parker Bridge Scholar Ansuman Satpathy, MD, PhD, PICI member Howard Chang, MD, PhD, PICI co-director Mark Davis, PhD, of Stanford University and their colleagues teamed up to create a new method called T-ATAC-seq to analyze the underlying genetic mechanisms of single T-cells to identify which cells are most capable of killing a tumor.

Why this is impactful to patients

Understanding T-cell biology is fundamental to the development of more effective immunotherapy treatments. “T-ATAC-seq is a useful technology that will help us better characterize T-cells, the dynamics of their response to tumors and how their function changes in response to immunotherapy,” says Pier Federico Gherardini, PhD, associate director of technology development at the Parker Institute. With this method, scientists can “link the identity of a T-cell, defined by the unique sequence of its T-cell receptor (TCR), with the T-cell’s functional state or capacity, as revealed by its epigenomic profile.”

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