|WORKING GROUP||Main Questions|
|I. Germline GENETIC Contributions TO Cancer Immune Responsiveness||
1. Which are the key molecular mechanisms involved in anti-tumor immunity that might be modulated by germline genetic variants?|
2. Are common genetic polymorphisms associated with a differential spontaneous or treatment-induced anti-tumor immune response?
3. How can we implement the study of host genetic diversity to identify novel biomarkers of responsiveness or toxicity to cancer immunotherapy?
|II. Somatic GENETIC Contributions TO Cancer Immune Responsiveness||
1. Can our knowledge of how cancer-intrinsic features influence the tumor microenvironment help us optimize immunotherapy combinations?|
2. How do we harmonize biomarkers derived from different technologies in order to specifically tailor IO therapy for a patient and increase the likelihood of response?
3. Will understanding the role of epigenetic re-programming downstream of molecular alterations in tumor cells reveal new opportunities to combat cancer immune-evasion strategies?
|III. Transcriptional Changes Related to CIR||
1. Can we generate transcriptional signature with high predictive value for a specific tumor-immune microenvironment?|
2. Can transcriptional profiling be developed as a biomarker for the CIR?
3. What technological advances do we need to dissect the tumor-immune microenvironment in space and time?
|IV. Immunogenic Cell Death and Cancer Immune Responsiveness||
1. What are the key molecular events that occur during immunogenic cell death that prime a robust immune response and promote immunological memory?|
2. Which therapeutic strategies will more effectively promote ICD while minimizing off target inhibition of immune responses?
3. How can detection of immunogenic cell death be routinely incorporated into clinical trials?
|V. Experimental Models of the Immune Landscape of Cancer||
1. What are the current limitations of humanized PDX mouse models?|
2. What approaches can be undertaken towards more faithful models of human cancer-human myeloid cells interface?
3. How to develop models that better model to reproduce tumor mutational load?