SC3 Introduction to The Tumour Microenvironment and Response to Cancer Immunotherapy
Monday November 12 | 9:00 – 12:00

Room Location: Room 5C

Mark Cragg, PhD, Professor, Experimental Cancer Biology, Antibody & Vaccine Group, Cancer Sciences Unit, University of Southampton

Frederick Arce Vargas, MD, PhD, MRCS, Group Leader, Translational Research, Autolus

The tumour microenvironment (TME) is a complex, dynamic environment in which extracellular matrix (ECM), soluble factors, immune cells, stromal cells and tumour cells interact. Each of these components is key to the establishment and growth of the tumour, as well as impacting tumour cell behaviour and response to treatment. For example, stromal cells such as fibroblasts and macrophages display tumour promoting properties, driving proliferation and survival whilst propagating an immunosuppressive environment. In this short course we will discuss the nature of the TME, how the tumour promotes an immunosuppressive environment and what opportunities this presents for reversing immune suppression to deliver effective immunotherapy.

During the course we will discuss:

• The constituents of the tumour microenvironment
• Factors in the TME that may influence therapeutic response such as checkpoint molecules and Fc gamma receptor expression
• Immune cell frequencies and phenotypes – suppressive macrophages, MDSCs, Tregs, cytokines
• Cross-talk between tumour and stromal cells – suppressive cytokines, influence on characteristics of tumour cells and ability to metastasise
• Extracellular matrix components: direct effects on immune cells, tumour cells and ability of agents to access tumour
• Vascularity, barriers to T cell entry
• Opportunities to overcome some of these factors including checkpoint blockers, strategies to re-polarise macrophages, strategies to block/modulate FcR expression (e.g. FcγRIIB blockers)
• Present a conceptual framework for how immunomodulatory mAb might best function
• Therapeutic success is likely to require combination approaches
• The importance of relevant model systems to assess drug candidates

Speaker Biographies

Mark Cragg, PhD, Professor, Experimental Cancer Biology, Antibody & Vaccine Group, University of Southampton

Mark Cragg is Professor of Experimental Cancer Biology in the Cancer Sciences Unit of Southampton University Faculty of Medicine. He obtained his PhD in 1998 and did his postdoctoral studies in Southampton with Martin Glennie and Melbourne, Australia with Andreas Strasser before returning to the UK to start his own group in 2007. He is interested in all aspects of how tumour regression can be induced and is focused on two main types of therapeutics – antibodies and small molecule inhibitors, with the aim of understanding how they elicit tumour cell destruction, how resistance occurs through changes in the microenvironment and how it might be overcome.

Frederick Arce Vargas, MD, PhD, MRCS, Group Leader, Translational Research, Autolus

Dr. Arce Vargas obtained a medical degree in the University of Costa Rica. He then moved to the United Kingdom where he obtained a PhD working with Prof. Mary Collins in UCL, where he worked on cancer vaccines using genetically modified dendritic cells. Following his interest in cancer immunotherapy, he then joined the labs of Sergio Quezada and Karl Peggs in the UCL Cancer Institute where his work focused on immune modulatory antibodies. He has recently moved as a group leader in Translational Research in Autolus, where he is working in immunotherapy with CAR-T cells.