Recent advances in cancer immunology and immunotherapy

Programme stream(s): Cancer discovery / underpinning research , Treatment
Programme session type(s): Recent Advances session

Chair: Sergio Quezada, University College London, UK
Speaker: Nicholas McGranahan, Francis Crick Institute, UK
Speaker: Burkhard Becher, University of Zurich, Switzerland
Speaker: Sine Reker Hadrup, Technical University of Denmark, Denmark

11:00-12:30

Room: Hall 1

The field of cancer immunology and immunotherapy is moving at a fast pace. In recent years we have seen a greater effort in multidisciplinary approaches aiming to understand cancer and immune cell co-evolution, response and resistance to therapy and to use that information to develop novel cutting edge therapeutics. This session will highlight the most recent work in this three areas of research within this exciting and rapidly evolving field. By the end of this session, delegates will: – Learn basic and translational aspect of cancer immunology including: 1. The use of bioinformatics and clinical samples to understand cancer and immune cell interactions in vivo 2. Development of novel biomarkers of response 3. Development of novel cancer immunotherapies.

GvHD: uncoupling immunopathology from the graft-vs-leukemia effect.
Speaker: Burkhard Becher
Affiliation: University of Zurich

Abstract:

Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective treatment for several hematologic malignancies, but can result in potentially life-threatening graft-versus-host disease (GvHD). GvHD is caused by T cells within the allograft attacking non-malignant host tissues; however, these same T cells mediate the therapeutic graft-versus-leukemia (GvL) response. Thus, there is an urgent need to understand how to mechanistically decouple GvL from GvHD. Here we show that the granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by allogeneic T cells exerts a distinct immune effector mechanism that separates the two processes. As such, GM-CSF drives GvHD pathology directly through engrafted phagocytes, producing inflammatory mediators such as IL-1β and ROS, leading to tissue damage. In contrast, GM-CSF had no impact on T cell activation or their capacity to eliminate leukemic cells, retaining undiminished GvL responses. Lastly, tissue and liquid biopsies from patients with grade IV GvHD showed an elevation of GM-CSF-producing T cells, suggesting that GM-CSF-neutralization has great translational potential in allo-HCT.