Kelly Bailey, MD, PhD

Understanding DNA damage and immunobiology to better treat bone sarcomas

Date/Time: Thursday, October 12 – 1:15 p.m.

Synopsis: Dr. Bailey’s talk will focus on the adolescent and young adult primary bone cancers Ewing sarcoma and osteosarcoma. Improving models to better understand bone sarcomas and preclinically test immunotherapies and modulators of the tumor microenvironment will be discussed. Thoughts on optimizing data and sample sharing between human trials, canine trials, and preclinical mouse trials to improve patient outcomes will be reviewed. Lastly, this bench to bedside to bench discussion will be wrapped up with a review of the current status of AOST2121, a human trial of a HER2-based maintenance immunotherapeutic for the treatment of relapsed osteosarcoma that was inspired by a trial utilizing this immunotherapy in canines with osteosarcoma.

About the presenter: Dr. Kelly Bailey is a physician scientist in the Division of Pediatric Hematology and Oncology at the UPMC Children’s hospital of Pittsburgh and an Assistant Professor of Pediatrics at the University of Pittsburgh School of Medicine. Dr. Bailey is the Co-Director of the Mario Lemieux Institute for Pediatric Cancer Research at UPMC Children’s. She is a pediatric oncologist specializing in the clinical treatment and biology of bone sarcomas, with a focus on the adolescent primary bone tumor Ewing sarcoma. She directs a laboratory-based research program and runs a Ewing sarcoma-focused outpatient clinic. Nationally, Dr. Bailey is a member of the Society for Pediatric Research. She holds leadership roles within the Children’s Oncology Group (COG), currently heading the Localized Ewing sarcoma Task Force, a group of 30+ national bone tumor experts tasked with developing the next national clinical trial for localized Ewing sarcoma. Dr. Bailey is also currently national Vice Chair for the COG clinical trial AOST2121, examining a maintenance immunotherapeutic for the treatment of relapsed osteosarcoma.

Dr. Christian Steidl

The tumor microenvironment of B cell lymphoma

Date/Time: Saturday, October 14 – 8:00 a.m.

Synopsis: Tumor microenvironment (TME) biology has been extensively explored in various lymphoma entities revealing significant and variable contributions of reactive immune cells to pathogenesis. Recent investigations e.g. in classic Hodgkin lymphoma, follicular lymphoma and diffuse large B cell lymphoma have also showed correlations of the TME composition and checkpoint protein expression with treatment outcome. The TME of B-cell lymphomas and, in particular, its composition and the spatial distribution of its components, can be perceived as a complex function of many factors, including altered genetic features of the malignant cells and aberrant molecular crosstalk between malignant and non-malignant cells mediated by receptor-ligand interactions and the release of cytokines and chemokines. Other host-specific factors include those involved in anti-tumor inflammatory responses or systemic immunocompetence.

In genomics studies, the cancer cells have been shown to undergo selection within their specific TME ‘ecosystems’ by mutation-based immune escape; e.g., by B2M and CIITA mutations resulting in loss of MHC-I / MHC-II expression, copy number amplification and rearrangement of PDL1 and PDL2 leading to T-cell anergy, and TNFRSF14 mutations restraining T-helper cell signals. Most recently, single cell RNA sequencing has broadened opportunities to describe the composition and cellular subsets in the TME. Synergistic to advances in single cell sequencing, multiplexed imaging techniques have added another dimension to describing cellular crosstalk in the context of the histology architecture of lymphomas. In this presentation, translational progress in our understanding of TME biology for biomarker development and improved treatment strategies will be discussed.

About the presenter: Dr Steidl is the Research Director of the Centre for Lymphoid Cancer at BC Cancer and Associate Professor in the Department of Pathology and Laboratory Medicine at the University of British Columbia. He has specific expertise in clinical malignant hematology, molecular pathology, genomics and lymphoma biology. Dr Steidl’s translational research group focuses on the pathogenesis of B cell lymphomas, tumor microenvironment biology and applied genomics.

Dr Steidl contributed to the discovery of novel somatic gene mutations in B cell lymphomas using next generation sequencing, and established microenvironment composition, and tumor-associated macrophages and normal B cells in particular, as novel biomarkers for outcome prediction in Hodgkin lymphoma.