Lymphoma SPORE

NCI Specialized Program of Research Excellence (Lymphoma SPORE)

National Cancer Institute SPORE Information

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Holden Comprehensive Cancer Center at The University of Iowa and Mayo Comprehensive Cancer Center
Co-Principal Investigators:
George J. Weiner, MD, The University of Iowa
Thomas E. Witzig, MD, Mayo Clinic

OVERALL ABSTRACT

The University of Iowa/Mayo Clinic (UI/MC) Lymphoma SPORE is a dynamic, productive, translational cancer research program based at two comprehensive cancer centers that was first funded in 2002 and competitively renewed in 2007, 2012, and most recently in 2017. At the center of the ongoing success of the UI/MC SPORE is the collaborative interaction among investigators at Iowa and Mayo, as well as SPORE basic laboratory, clinical, and population-based investigators. The overall goal of the SPORE is to support innovative, interactive, translational research into lymphoma and chronic lymphocytic leukemia that leverages the expertise of laboratory, clinical, and population-based research at both institutions. The SPORE has been highly productive as demonstrated by:

  • Identification of new tumor markers
  • Scientific findings that led to additional translational lymphoma grants from the NCI
  • Multiple publications, including many authored by investigators from both institutions
  • Brisk accrual to translational clinical trials
  • Discoveries that have changed clinical practice in the care of patients with lymphoma

The UI/MC Molecular Epidemiology Resource is based in the SPORE, and serves as a vital resource for both SPORE research and research projects supported by other grants.

The current program builds on past successes and supports four major research projects that represent new concepts that emerged from research supported over the past funding period.

Major SPORE projects are as follows:

  1. Activating Phagocytic Macrophages in non-Hodgkin Lymphoma
  2. Microenvironment Modification and Anti-PD1 Immunotherapy of Lymphoma
  3. Targeting Tumor Metabolism in Lymphoma
  4. Genomic Predictors of Early Relapse in Immunochemotherapy-Treated Follicular Lymphoma

Support will also be provided to pursue novel translational concepts in lymphoma research and new investigators through the Developmental Research Program and Career Enhancement Program. Finally, the SPORE will enhance the infrastructure that supports translational lymphoma research at both institutions through shared core resources in:

 

PROJECT 1: Activating Phagocytic Macrophages in non-Hodgkin Lymphoma

Project Leaders: Stephen Ansell, MD, PhD (Mayo) and Andrew Feldman, MD (Mayo)
Co-Investigators: Grzegorz Nowakowski, MD (Mayo), Zhi Zhang Yang, MD (Mayo), and Umar Farooq, MD (Iowa)

Macrophage-mediated phagocytosis is an important mechanism to eliminate diseased and malignant cells. Malignant lymphoma cells, by overexpressing CD47, provide a ‘don't-eat-me’ signal and thereby avoid eradication. We propose to block CD47/SIRPα signaling to restore an ‘eat-me’ message. However, not all macrophages in lymphoma tumors express SIRPα and we have defined populations that are CD14+SIRPαhigh and those that are CD14-SIRPαlow/-. We therefore propose to determine the function of these two populations, to determine whether the innate phagocytic immune system targets lymphoma cells, and test whether blocking an innate immune checkpoint (CD47/SIRPα signaling) improves the anti-tumor immune response.

PROJECT 2: Microenvironment Modification and Anti-PD1 Immunotherapy of Lymphoma

Project Leaders: George Weiner, MD, PhD (Iowa) and Yi Lin, MD, PhD (Mayo)
Co-Investigator: Brian Link, MD (Iowa), Jon Houtman, PhD (Iowa), Haidong Dong, MD, PhD (Mayo), and Umar Farooq (Iowa)

Growing evidence suggests development of a robust anti-tumor immune response can be enhanced by modifying the tumor microenvironment in a manner that enhances release, uptake, and presentation of tumor antigens to T cells. This project will explore two distinct strategies of tumor microenvironment modulation combined with checkpoint inhibitor to enhance anti-lymphoma response. The first involves intra-tumoral injection of autologous dendric cells into a cryoablated tumor; the second involves injection of a tumor with a virus-like particle containing immunostimulatory DNA.

PROJECT 3: Targeting Tumor Metabolism in Lymphoma

Project Leaders: Thomas E. Witzig, MD (Mayo) and Gail Bishop, PhD (Iowa)
Co-Investigators: Laura Stunz, PhD (Iowa), Xiaosheng Wu, MD (Mayo), and Daniel Billadeau, PhD (Mayo)

This project is focused on developing new treatments for lymphoma that aim to interfere with signal pathways that drive the use of glucose. Some lymphomas lose a regulator of growth called TNFR-associated factor 3 (TRAF3) and activate a regulator of many pathways (including glucose) called glycogen synthase kinase 3 (GSK3). We are planning for the first time to test a new GSK3 inhibitor to learn if it can inhibit lymphoma tumor growth and survival in patients.

PROJECT 4: Genomic Predictors of Early Relapse in Immunochemotherapy-Treated Follicular Lymphoma

Project Leaders: James Cerhan, MD, PhD (Mayo), Anne Novak, PhD (Mayo), and Brian Link, MD (Iowa)
Co-investigator: Lisa Rimsza, MD (Mayo)

Follicular lymphoma is the most common indolent non-Hodgkin lymphoma and has a highly variable clinical course. Currently, mainly clinical factors are used to identify high versus low risk patients and to predict overall survival, but with modest utility. This will be the first study to systematically discover, validate, and integrate clinical, tumor, and host genetic biomarkers into useful clinical information focused on follicular lymphoma patients with early clinical failures.

Core Areas

Administration

George J. Weiner, MD (Iowa) and Thomas Witzig, MD (Mayo)

The overall goal of the University of Iowa/Mayo Clinic Lymphoma SPORE Administration Core is to stimulate research in lymphoma and to expedite the translation of discoveries into new and better methods of prevention, detection, and treatment of lymphoma.

Biospecimens Core

Andrew Feldman, MD (Mayo) and Sergei Syrbu, MD (Iowa)

Effective lymphoma research requires blood and tumor tissue for translational research. The Biospecimens Core coordinates all specimen-related research for projects in the Lymphoma SPORE. This core has developed new innovations in Biospecimens Core sampling (stool microbiome) and novel techniques (CyTOF) that will enable investigators to expand lymphoma research in the next funding period.

Biostatistics and Bioinformatics

Brian Smith, PhD (Iowa) and Susan Slager, PhD (Mayo)

Robust Biostatistics and Bioinformatics is critical for the conduct of effective translational lymphoma research in the SPORE. The Biostatistics and Bioinformatics Core provides this expertise through full collaboration of Biostatisticians and Bioinformaticists in all SPORE research projects and for investigators receiving Developmental Research and Career Enhancement Awards.

Clinical Research Core

Thomas Habermann, MD (Mayo) and Brian Link, MD (Iowa)

The goal of the Clinical Research Core is to support clinical research generated by SPORE investigators for patients with lymphoma. This includes investigations into factors such as lifestyle, exposures, and genetic factors that may cause lymphoma, and tumor factors that predict response to treatment and survival. Lastly, this core works with investigators and patients on new treatments aiming to improve lymphoma outcomes.

Career Enhancement Program

Jon Houtman, PhD (Iowa) and Scott Kaufmann, MD, PhD (Mayo)

The purpose of the Career Enhancement Program is to support and mentor young investigators at the junior faculty level so that they can become outstanding translational investigators with a primary focus on lymphoma. The Lymphoma SPORE selects two outstanding candidates each year for support. Candidate success is enhanced through mentorship and access to the SPORE Core resources.

Developmental Research Program

Steven Lentz, MD, PhD (Iowa) and Stephen J. Russell, MD, PhD (Mayo)

The SPORE Lymphoma Developmental Research Program provides funding for innovative lymphoma research that can benefit from the unique resources provided by the SPORE. The program encourages proposals from investigators in related disciplines so as to rapidly translate new treatment concepts to patients.

Patient Advocates

Lorraine Dorfman (Iowa), Benjamin Haines (Mayo), Richard Noeth (Iowa), and Robert Paschke (Mayo)

Patient advocates play a central role in the SPORE and provide a patient’s perspective on all aspects of the SPORE program. Patient advocates participate in SPORE meetings such as the monthly SPORE videoconference and annual face-to-face meeting.