Brain Tumor Funders’ Collaborative
November 8-10, 2017
Sheraton at Westport, St. Louis, MO 63146

Immunotherapy for Glioma: Making Good on the Promises?

Identifying ways to harness our innate immune systems against cancer cells has been a long-sought goal in oncology.    Unfortunately progress against this goal was limited during much of the 20th century.     In the past 20 years, however, two promising lines of research have breathed new life into the hope for immunotherapies for cancer.  The promising lines of research are the use of check-point inhibitors that block the immune-suppressive protein PD-1 and adoptive T-cell therapies.   Both are demonstrating some success (and some failures) in the clinical setting.     For example, the check-point inhibitors Keytruda (pembrolizumab) or Opdivo (nivolumab) do not work for many patients due to a variety of factors, and clinical trials are likely failing because the design has been too simple given the complexity of the human immune system.  One factor could be that the cancer-killing T cells of some individual cancer patients fail to proliferate and launch an effective response.  Even if they do proliferate, another factor contributing to the failure of check-point inhibitors could be a lack of T-cell trafficking and infiltration.   Similarly, adoptive T-cell therapies have demonstrated success in the laboratory that fails to transfer into the clinical setting.   Tumors evolve escape routes.  A recent review by Theresa Whiteside and her colleagues (Clin Cancer Res; 22(8); 1845-55, 2016) provides an excellent summary of the opportunities and challenges on immunotherapy. Lessons learned from these early trials can (and should) inform neuro-oncological approaches as should the knowledge from research studies and clinical investigations in non-oncological neurological conditions.  

That immunotherapies have difficulty transferring from the experimental to the clinical oncology context should be unsurprising. Both the immune system and the tumor microenvironment are complex, dynamic, adaptive systems responding to perturbations via a number of feedback and feedforward loops.   The multiscale interactions of each individual’s immune system with the tumor and vice versa makes controlled interventions difficult to manage and the behavior of the systems difficult to predict.   

These complexities common to all cancer systems are compounded by the unique characteristics of immune reactions in the central nervous system and the complicated cellular heterogeneity of the brain tumor ecosystem.   It is critical that attempts to design immunotherapy for brain tumors build on a thorough understanding of how immunotherapies will succeed in the context of the human brain and furthermore in the context of different treatments.

The November 2017 Brain Tumor Funders Collaborative educational workshop will focus on the following topics and questions:

• What is the potential of immunotherapy in the pediatric setting?   What do we need to know about immunity in the context of a developing brain?   What are the risks over a life-time?  Are there particular pediatric brain tumors best suited for immunologic approaches?     What is the potential for identifying biomarkers that are predictive of the desired response in pediatric patients?
• What is known about the role of the innate immune system in the development of low grade gliomas and in the progression to high grade gliomas?   Could treatment with immunotherapies in the low grades cases result in high grade gliomas resistant to immunological approaches? 
• What are the opportunities and pitfalls of immune-therapies in adult gliomas?  Are we considering what we know about immune system complexities and the promises and pitfalls of immune reactions in normal brain and in other neurological diseases in the design of clinical trials for brain tumor?   What effect could immune-senescence have in the ability of an aging patient to mount the necessary immune response? How might heavily pre-treated patients respond differently than treatment naïve patients?
• How to best use new and available data sets to help inform and advance the research/clinical agenda?

Agenda

 

Wednesday, November 8 
5:30 – 6:30 pm             Reception, Plaza Ballroom 4&5
6:30 – 8:30 pm             Buffet Dinner, Plaza Ballroom 4&5

 

Thursday, November 9
8:00 am                        Continental Breakfast, Outside Conference Room C
8:55 am                        Welcome, Conference Room C

 

Please note: talks are informal and intended to stimulate discussion and conversation.  All participants are expected to engage, ask questions, raise issues and generate new ideas.   Speakers should not plan to fill their allotted time with a formal presentation.  

9:00 am                        Session 1 - Understanding Immuno-Complexity
9:00 – 10:00                 Setting the stage with an (a) neuro-immunology primer relevant to disease states including brain tumor  
Robyn Klein, Washington University School of Medicine

10:15 –11:15               The life-trajectory of the immune system (including immuno-senescence)
Jean Carlson, University of California, Santa Barbara

11:30 am                      Session 2 - Immunotherapies in different patient populations: Challenges and Opportunities

11:30 – 12:30               What are we learning from immunotherapy trials in adult?    
Amy Heimberger, MD Anderson Cancer Center

12:45pm                       Lunch, Terrace Restaurant

2:00 pm                        Session 2 - Immunotherapies in different patient populations: Challenges and Opportunities

2:00 – 3:00                  Overview on current opportunities for immunotherapy in pediatric glioma
Duane Mitchell, University of Florida

3:15 – 4:15                  What is the role of the immune system in low grade to high grade glioma transitions and where is there the likeliest potential for successful immunotherapies? 
David Reardon, Dana-Farber Cancer Institute

                                    Departures

6:00 pm                        Reception and Dinner for BTFC reps, other funders, and other invited guests whose travel plans allow.   Alpine Room 1, Westport Chalet Hotel

 

Friday, November 10
8:00 am                        Continental Breakfast, Outside Conference Room C
9:00 am                        Funders Only:  Follow Up Discussions and Future Plans, Conference Room C
12:00 pm                      Lunch, Terrace Restaurant

 

Departures

 

 

Participant List

 

Jean Carlson, University of California, Santa Barbara
M. Brent Dolezalek, James S. McDonnell Foundation
David Eisenstat, University of Alberta
Susan Fitzpatrick, James S. McDonnell Foundation
Amy Heimberger, MD Anderson Cancer Center
Robyn Klein, Washington University School of Medicine
Brian Knox, James S. McDonnell Foundation 
Shandra Koler, Sontag Foundation
Susan Marshall, Brain Tumour Foundation of Canada
Joe Megyesi, Brain Tumour Foundation of Canada
Tom Mikkelsen, Ontario Brain Institute
Duane Mitchell, University of Florida
Hideho Okada, University of California, San Francisco
David Reardon, Dana-Farber Cancer Institute
Joanne Salicido, Pediatric Brain Tumor Foundation
Leslie Stokes, American Brain Tumor Association
Kay Verble, Sontag Foundation
Nicole Willmarth, American Brain Tumor Association
Pat Yuzawa-Rubin, Circle of Service Foundation