The beautiful spring in Philadelphia provided an inspiring setting for the 2015 Annual Meeting of the American Association for Cancer Research (AACR) and the nearly 20,000 scientists who gathered to share the latest advances aimed at understanding and ultimately conquering cancer. The conference held April 17-22, hosted basic, translational, clinical and population-based cancer researchers from across the globe, and featured scientific presentations from the top scientists from all areas of cancer research.
Work from more than 45 investigators from the University of Chicago Medicine Comprehensive Cancer Center was featured as oral or poster presentations, underscoring the fact that many of our faculty are pre-eminent leaders of their respective fields. Additionally, many of our brightest graduate and medical students, as well as postdoctoral fellows, made a splash on this international stage. Although we cannot cover everything here, specific areas that were focal points of the meeting in which our faculty and trainees presented their latest findings included tumor immunology, metastasis, epigenetics, breast cancer, clinical trials and targeted therapy.
Tumor Immunology. Because of recent progress in treating cancer through modulation of the immune system, one of the areas that generated the most buzz at the AACR Annual Meeting was tumor immunology. Thomas Gajewski, MD, PhD, professor of pathology and medicine, chaired a session on “Biomarkers for Immunotherapy Response” and presented findings from his laboratory aimed at understanding why some patients respond to immunotherapies and others do not. He described a novel innate immune sensing pathway that drives T cell priming mediated by stimulator of interferon genes (STING) and interferon beta, as well as the development of STING agonists for cancer therapy. He also identified somatic mutations in the CTNNB1 gene encoding the Wnt signaling effector beta-catenin and showed that mutant beta-catenin controls the T-cell inflamed microenvironment in tumors and dictates how they respond to immunotherapy.
In a major symposium talk, Yang-Xin Fu, MD, PhD, Fanny L. Pritzker Professor of Pathology, presented his work on identifying mechanisms contributing to the enhanced therapeutic benefit of combining immunotherapy with radiation therapy and the mechanisms underlying radiation resistance, including the STING/interferon pathway.
Stephen Kron, MD, PhD, professor of molecular genetics and cell biology, spoke in an educational session and discussed strategies to more efficiently target tumors with nanoparticles and immunotherapy using a radiation-enhanced permeability and retention method that his group developed.
Noura Choudhury, a medical student in the laboratory of Yusuke Nakamura, MD, PhD, professor of medicine, collaborating with Peter O’Donnell, MD, assistant professor of medicine and Gary Steinberg, MD, Bruce and Beth White Family Professor of Surgery, presented a poster demonstrating that bladder cancers with more somatic mutations had reduced T cell diversity (that is, they showed clonal expansion of certain T cell populations) and reduced likelihood of tumor recurrence. On a related front, Justin Kline, MD, assistant professor of medicine, in collaboration with Nakamura and Sonali Smith, MD, professor of medicine, observed an oligoclonal expansion of regulatory T cells in follicular lymphoma tissues compared to normal lymph nodes and an inverse correlation between the diversity of regulatory T cells and CD8-positive T cells in follicular lymphoma.
Daniel Catenacci, MD, assistant professor of medicine, presented a poster developing tools to measure biomarkers in immunotherapy, in this case a quantitative mass spectrometric assay for PD-L1 levels in non-small cell lung cancer, as well as bladder, breast, and gastric cancer.
Breast Cancer. Several Comprehensive Cancer Center breast cancer researchers took center-stage at the conference. Olufunmilayo Olopade, MBBS, Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics, chaired and spoke in an educational session and described her groups’ efforts in screening young women with breast cancer from the African Diaspora and African-American women on the South Side of Chicago for BRCA1 and BRCA2 mutations and identifying other genetic modifiers of risk. Olopade also gave a talk on genotype-phenotype correlations in diverse populations, and posters from her laboratory described breast cancer subtypes in circulating miRNA profiles, a novel strategy to inhibit BRCA1 hypermethylation to restore expression, and the role of T cells in breast cancer subtypes.
Rita Nanda, MD, assistant professor of medicine, collaborated with Olopade on the T cell study, but also was involved in multi-institutional clinical studies aimed at understanding resistance to HER2-targeted therapies.
Payal Tiwari, a PhD student under the mentorship of Marsha Rosner, PhD, Charles B. Huggins Professor in the Ben May Department for Cancer Research, gave an oral presentation on her work addressing the role of metabolically activated macrophages from the breast cancer microenvironment in promoting tumor initiation and invasion. This project is the result of a collaboration with Lev Becker, PhD, assistant professor in the Ben May Department for Cancer Research, and Swati Kulkarni, MD, associate professor of surgery.
Kay Macleod, PhD, associate professor in the Ben May Department for Cancer Research, chaired a major symposium on “Autophagy and Cancer” and presented her investigation of contrasting tumor-associated consequences of defects in autophagy (i.e., the turnover of cellular organelles and content) and mitophagy (i.e., the self-eating of mitochondria specifically). Among other tumor models, Macleod showed that the loss of the mitophagy regulator BNIP3 accelerated tumor growth and metastasis in a pre-clinical breast cancer model.
Diana West, PhD, a postdoctoral fellow in the laboratory of Suzanne Conzen, MD, professor of medicine, presented her work on the glucocorticoid receptor (GR) in breast cancer in a mini symposium talk. She described an unexpected association between GR and the estrogen receptor (ER) such that GR activation in GR- and ER-positive breast cancers may modulate the activity of ER, including regulation of pro-proliferative and anti-apoptotic gene expression.
In a poster presentation, work from Geoffrey Greene, PhD, Virginia and D.K. Ludwig Professor and Chair of the Ben May Department for Cancer Research, and PhD student Anna Dembo, demonstrated that hormone replacement therapy formulations suppress tumor development in preclinical models through complex regulation of estrogen receptor (ER)-mediated gene expression.
Metastasis. Progress in understanding and combatting the metastatic spread is critical to improving patient outcomes and was featured prominently at the AACR Annual Meeting.
Ralph Weichselbaum, MD, D.K. Ludwig Professor of Radiation & Cellular Oncology/Distinguished Service Professor, participated in a session on “Recent Advances in Diagnostics and Therapeutics Research, ” and discussed his latest work dissecting the cellular and molecular pathways driving oligometastasis, or a limited number of metastases.
Work from the laboratory of Rosner was presented in a poster by PhD student Daniel Rabe. They demonstrated that the metastasis suppressor RKIP regulates the tumor microenvironment, in this case breast cancer, by blocking recruitment of pro-metastatic tumor-associated macrophages.
Clinical Trials, Outcomes and Risk. Every year at the AACR Annual Meeting, increasingly more emphasis is put upon clinical research, as well as issues around patient care and survivorship. In the area of clinical trial design and care, Mark Ratain, MD, Leon O. Jacobson Professor of Medicine, chaired and spoke in a session on “Dose Optimization for 21st Century Oncology Drugs” and described efforts in optimizing therapeutic dose selection in phase II trials.
Philip Connell, MD, associate professor of radiation and cellular oncology, gave an oral presentation on his work devising a method to measure DNA repair in tumors called the recombination proficiency score (RPS). RPS quantification is based on the expression of four genes involved in DNA repair preference, and his group showed that RPS-low tumors have more mutations and aggressive clinical features, as well as being hypersensitive to chemotherapy.
Tara Henderson, MD, assistant professor of pediatrics, participated in an educational session in which she discussed the challenges faced by survivors of childhood cancer from the standpoints of the patients, physicians and health care systems.
Brandon Pierce, PhD, assistant professor of public health sciences, chaired a minisymposium entitled “Molecular and Genetic Epidemiology of Cancer 4: New Insights.” Additionally, a poster from his student Molly Scannell Bryan, in collaboration with Habibul Ahsan, MBBS, Louis Block Professor of Public Health Sciences, described a study of exonic variants of three genes, ZMIZ1, FGF3 and ANKLE1, and examined their effect on ER-negative breast cancer risk.
One of the highlights of the conference for trainees is the host of career development sessions offered. Student and Associate Member Council member Colles Price moderated a session on “Effective Communication with Peers and the Public.” Kathleen Goss, PhD, senior science writer and director for strategic partnerships of the Comprehensive Cancer Center, was one of the featured speakers, specifically focusing her remarks on communicating science with a broad audience.
Also announced at the conference was the creation of a second ovarian cancer dream team focused on “DNA Repair Therapies for Ovarian Cancer,” funded by Stand Up To Cancer, the Ovarian Cancer Research Fund, the Ovarian Cancer National Alliance, and the National Cancer Coalition. Although the lead academic sites are the Dana-Farber Cancer Institute and University of Washington, Comprehensive Cancer Center investigator Gini Fleming, MD, professor of medicine, will be leading efforts here testing PARP inhibitors in clinical trials.
Additional posters that were presented at the conference included work from Nakamura; Mark Lingen, DDS, PhD; Tanguy Seiwert, MD; Everett Vokes, MD; Ravi Salgia, MD; Kevin White, PhD; Walter Stadler, MD; Jason Luke, MD; Donald Vander Griend, PhD; Ahsan; Chuan He, PhD; Macleod; Wendy Stock, MD; Dezheng Huo, MD, PhD; Catenacci; Olatoyosi Odenike, MBBS; Gordana Raca, MD, PhD; Ernst Lengyel, MD, PhD; Sonia Kupfer, MD; Kenan Onel, MD, PhD; Todd Zimmerman, MD; Brian Chiu, PhD; Fleming; Yoav Gilad, PhD; and Thomas Krausz, MD.