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Published Research

Great science gets published

Our investigators publish game-changing research in the world’s leading scientific journals. From basic research to clinical studies, their work influences others in the field and is a springboard for new studies that move us one step closer to cures for cancer. PICI investigators publish thousands of papers a year, often in collaboration with each other. Here we highlight some of their best work.

2.2K

Research Papers Published

421

Journals

136

Multi-Institutional Papers

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Showing 1 - 10 of 25 Publications

Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells

June 17, 2020 | Cell

Megan K. Ruhland, Edward W. Roberts, En Cai, Adriana M. Mujal, Kyle Marchuk, Casey Beppler, David Nam, Nina K. Serwas, Mikhail Binnewies, Matthew F. Krummel

Intratumoral CD4 + T Cells Mediate Anti-tumor Cytotoxicity in Human Bladder Cancer

June 3, 2020 | Cell

David Y. Oh, Serena S. Kwek, Siddharth S. Raju, Tony Li, Elizabeth McCarthy, Eric Chow, Dvir Aran, Arielle Ilano, Chien-Chun Steven Pai, Chiara Rancan, Kathryn Allaire, Arun Burra, Yang Sun, Matthew H. Spitzer, Serghei Mangul, Sima Porten, Maxwell V. Meng, Terence W. Friedlander, Chun Jimmie Ye, Lawrence Fong

Systemic dysfunction and plasticity of the immune macroenvironment in cancer models

May 25, 2020 | Nature Medicine

Breanna M. Allen, Kamir J. Hiam, Cassandra E. Burnett, Anthony Venida, Rachel DeBarge, Iliana Tenvooren, Diana M. Marquez, Nam Woo Cho, Yaron Carmi & Matthew H. Spitzer

Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors

April 27, 2020 | Nature Medicine

Johanna Theruvath, Elena Sotillo, Christopher W. Mount, Claus Moritz Graef, Alberto Delaidelli, Sabine Heitzeneder, Louai Labanieh, Shaurya Dhingra, Amaury Leruste, Robbie G. Majzner, Peng Xu, Sabine Mueller, Derek W. Yecies, Martina A. Finetti, Daniel Williamson, Pascal D. Johann, Marcel Kool, Stefan Pfister, Martin Hasselblatt, Michael C. Frühwald, Olivier Delattre, Didier Surdez, Franck Bourdeaut, Stephanie Puget, Sakina Zaidi, Siddhartha S. Mitra, Samuel Cheshier, Poul H. Sorensen, Michelle Monje & Crystal L. Mackall

Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies

April 16, 2020 | Cell

Theodore L. Roth, P. Jonathan Li, Franziska Blaeschke, Jasper F. Nies, Ryan Apathy, Cody Mowery, Ruby Yu, Michelle L.T. Nguyen, Youjin Lee, Anna Truong, Joseph Hiatt, David Wu, David N. Nguyen, Daniel Goodman, Jeffrey A. Bluestone, Chun Jimmie Ye, Kole Roybal, Eric Shifrut, Alexander Marson

CRISPR-engineered T cells in Patients with Refractory Cancer

February 28, 2020 | Science

Edward A. Stadtmauer, Joseph A. Fraietta, Megan M. Davis, Adam D. Cohen, Kristy L. Weber, Eric Lancaster, Patricia A. Mangan, Irina Kulikovskaya, Minnal Gupta, Fang Chen, Lifeng Tian, Vanessa E. Gonzalez, Jun Xu, In-young Jung, J. Joseph Melenhorst, Gabriela Plesa, Joanne Shea, Tina Matlawski, Amanda Cervini, Avery L. Gaymon, Stephanie Desjardins, Anne Lamontagne, January Salas-Mckee, Andrew Fesnak, Donald L. Siegel, Bruce L. Levine, Julie K. Jadlowsky, Regina M. Young, Anne Chew, Wei-Ting Hwang, Elizabeth O. Hexner, Beatriz M. Carreno, Christopher L. Nobles, Frederic D. Bushman, Kevin R. Parker, Yanyan Qi, Ansuman T. Satpathy, Howard Y. Chang, Yangbing Zhao, Simon F. Lacey, Carl H. June

ILC2s amplify PD-1 Blockade by Activating Tissue-specific Cancer Immunity

February 19, 2020 | Nature

John Alec Moral, Joanne Leung, Luis A. Rojas, Jennifer Ruan, Julia Zhao, Zachary Sethna, Anita Ramnarain, Billel Gasmi, Murali Gururajan, David Redmond, Gokce Askan, Umesh Bhanot, Ela Elyada, Youngkyu Park, David A. Tuveson, Mithat Gönen, Steven D. Leach, Jedd D. Wolchok, Ronald P. DeMatteo, Taha Merghoub & Vinod P. Balachandran

B cells and tertiary lymphoid structures promote immunotherapy response

January 15, 2020 | Nature

Beth A. Helmink, Sangeetha M. Reddy, Jianjun Gao, Shaojun Zhang, Rafet Basar, Rohit Thakur, Keren Yizhak, Moshe Sade-Feldman, Jorge Blando, Guangchun Han, Vancheswaran Gopalakrishnan, Yuanxin Xi, Hao Zhao, Rodabe N. Amaria, Hussein A. Tawbi, Alex P. Cogdill, Wenbin Liu, Valerie S. LeBleu, Fernanda G. Kugeratski, Sapna Patel, Michael A. Davies, Patrick Hwu, Jeffrey E. Lee, Jeffrey E. Gershenwald, Anthony Lucci, Reetakshi Arora, Scott Woodman, Emily Z. Keung, Pierre-Olivier Gaudreau, Alexandre Reuben, Christine N. Spencer, Elizabeth M. Burton, Lauren E. Haydu, Alexander J. Lazar, Roberta Zapassodi, Courtney W. Hudgens, Deborah A. Ledesma, SuFey Ong, Michael Bailey, Sarah Warren, Disha Rao, Oscar Krijgsman, Elisa A. Rozeman, Daniel Peeper, Christian U. Blank, Ton N. Schumacher, Lisa H. Butterfield, Monika A. Zelazowska, Kevin M. McBride, Raghu Kalluri, James Allison, Florent Petitprez, Wolf Herman Fridman, Catherine Sautès-Fridman, Nir Hacohen, Katayoun Rezvani, Padmanee Sharma, Michael T. Tetzlaff, Linghua Wang & Jennifer A. Wargo

MHC-II neoantigens shape tumour immunity and response to immunotherapy

October 23, 2019 | Nature

Elise Alspach, Danielle M. Lussier, Alexander P. Miceli, Ilya Kizhvatov, Michel DuPage, Adrienne M. Luoma, Wei Meng, Cheryl F. Lichti, Ekaterina Esaulova, Anthony N. Vomund, Daniele Runci, Jeffrey P. Ward, Matthew M. Gubin, Ruan F. V. Medrano, Cora D. Arthur, J. Michael White, Kathleen C. F. Sheehan, Alex Chen, Kai W. Wucherpfennig, Tyler Jacks, Emil R. Unanue, Maxim N. Artyomov & Robert D. Schreiber

Summary of work

The cancer immunotherapy field has largely focused on activating killer T cells to attack cancer, however many patients do not respond to this approach. A new study from Washington University School of Medicine in St. Louis published in Nature has revealed for the first time that helper T cells could be the missing puzzle piece in cancer immunotherapy.

“Just because killer T cells might be present around the tumor, doesn’t mean they’re actively killing tumors. We found that not only do you need helper T cells to recruit the killer T cells, the helper cells need to be there to coax the killer T cells to mature into an active state in which they are capable of killing [cancer] cells,” said first author Elise Alspach, PhD, a postdoctoral research associate in the lab of PICI investigator Robert Schreiber, PhD.

They believe an approach that combines checkpoint inhibitor with a cancer vaccine that specifically activates helper T cells could be a winning solution for many p­­atients. The researchers have only studied the combination in mice so far, but they aim to test the treatments in patients.

Why this is impactful to patients

This pivotal paper pulls back the curtain on the role of the helper T cell. Until now, helper T cells have been overshadowed by cancer immunotherapy’s star player, the killer T cell. Scientists now realize that helper T cells might play a near equally important role.

In fact, after treatment with checkpoint blockade therapy, a successful immune response depends on both helper T cell and killer T cell activation in tumors that don’t respond to the immunotherapy alone.

“In the past we’ve centered our thinking on what molecules are going to drive killer T cells into a tumor. This research prompts us to think about how we can we prime helper T cells as well,” said PICI researcher Danny Wells.

In terms of treatment options, “it opens up the realms for checkpoint inhibitors and cancer vaccines. We need to be considering both. It changes how we think about using checkpoint inhibitors entirely,” Wells notes.

A major challenge to understand the role of helper T cells for immunotherapy has been identifying the mutant proteins, or neoantigens, that trigger a response. The authors of this study are using a software they created to chip away at this problem.

And while we are still a ways off from seeing this approach in the clinic, this is a promising approach to defeat cancers resistant to immunotherapy.

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

October 17, 2019 | New England Journal of Medicine

James Larkin, Vanna Chiarion-Sileni, Rene Gonzalez, Jean-Jacques Grob, Piotr Rutkowski, Christopher D. Lao, C. Lance Cowey, Dirk Schadendorf, John Wagstaff, Reinhard Dummer, Pier F. Ferrucci, Michael Smylie, David Hogg, Andrew Hill, Ivan Márquez-Rodas, John Haanen, Massimo Guidoboni, Michele Maio, Patrick Schöffski, Matteo S. Carlino, Céleste Lebbé, Grant McArthur, Paolo A. Ascierto, Gregory A. Daniels, Georgina V. Long, Lars Bastholt, Jasmine I. Rizzo, Agnes Balogh, Andriy Moshyk, F. Stephen Hodi, and Jedd D. Wolchok

Summary of work

In a 5-year follow-up with patients with advanced melanoma, patients who received nivolumab plus ipilimumab or nivolumab alone tended to live longer and their tumors progressed more slowly than those who received ipilimumab alone.

Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. Five-year progression-free survival was 36%, 29%, and 8% in the nivolumab-plus-ipilimumab, nivolumab, and ipilimumab groups, respectively.

There was no sustained decline of health-related quality of life during or after treatment with the immunotherapy regimen. No new late toxic effects were observed in this study.

Co-senior authors on the paper include PICI researchers F. Stephen Hodi, MD and co-director Jedd Wolchok, MD, PhD.

Why this is impactful to patients

“10 years ago, only one in twenty patients with advanced melanoma survived beyond five years. This impressive research demonstrates that this immunotherapy combination increases the chances of a patient surviving advanced melanoma significantly.” says Leo Nissola, MD, a senior clinical scientist at PICI.

The study has great impact for the field as well. “This was the first trial to use two immunotherapies in tandem to treat a disease. And, this five year milestone is the longest phase 3 follow-up of a combination therapy.”

The jury is still out on whether the combination therapy or nivolumab alone is a better option for patients. However, the research affirms that two good options now exist outside of chemotherapy.

“It is exciting progress,” said Dr. Nissola.