The tumour immune microenvironment (TIME) plays a critical role in the evolution and progression of cancer. TIME is a highly complex and heterogeneous system that encompasses cells of the immune system and their interactions with the tumour microenvironment. The balance of suppressive versus cytotoxic responses in the tumour microenvironment is balanced by TIME and this can influence disease outcome, with high levels of T cell infiltration associated with better survival in patients. In this series, we explore the impact of TIME on response to cancer treatment and how certain treatments can alter the composition of the TIME and be used in combination with immunotherapy to improve patient outcome.
Join us on 30th November at 10am GMT for the final episode in this three-part series with Dr Aideen Ryan, University of Galway.
- Dr Florent Petitprez, University of Edinburgh, 30th November 10am GMT, B cells, tertiary lymphoid structures, and response to cancer immunotherapy
- Dr Eleanor Cheadle, University of Manchester, 7th December 10am GMT, Investigating how radiotherapy affects the tumour immune microenvironment
- Dr Aideen Ryan, University of Galway, 14th December 10am GMT, Stromal cells and immunosuppression in the tumour microenvironment
The motivation behind our research arises from the limited efficacy of immunotherapies in stromal-dense tumour microenvironments (TME). T-cell based immunotherapies, including immune checkpoint inhibitors and CAR T cell therapies, are approved backbone therapies for many blood cancers and some solid malignancies. However, T-cell based immunotherapies in solid stromal-dense tumours such as pancreatic, multiple myeloma and colorectal cancers have shown only limited success indicating that their optimization requires a deeper understanding of the immunosuppressive mechanisms that dominate these tumour landscapes. Stromal cells, including mesenchymal stromal cells and cancer-associated fibroblasts, sense and switch inflammation to maintain homeostasis in the body. In the TME, they are recognized as a major obstacle for immunotherapies as they play a key role in immune suppression; however, the mechanisms underlying this are not fully understood.
In this presentation, I will summarise some of our recent findings where we identify novel mechanisms of immunosuppression, including stromal cell immune checkpoints and sialic acid – siglec interactions that can result in immune cell dysfunction. This knowledge may pave the way for the development of more efficient stromal cell targeted immunotherapies for the treatment of cancer. Using representative models of tumours that arise in stromal-dense microenvironments, we demonstrate that tumour-induced stromal cells can dictate anti-tumour immune responses and may represent a therapeutic target in cancer.
Keywords: Stromal cells, immunotherapy, anti-tumour immune responses, PD-L11, immunosuppression, colorectal cancer
- Colton M, Cheadle EJ, Honeychurch J, Illidge TM. Reprogramming the tumour microenvironment by radiotherapy: implications for radiotherapy and immunotherapy combinations. Radiat Oncol. 2020. 15(1):254
- Cheng S, Cheadle EJ, Illidge TM. Understanding the effects of radiotherapy on the tumour immune microenvironment to identify potential prognostic and predictive biomarkers of radiotherapy response. Cancers 2020 12(10):2835
To speak at a Researcher Live session, please email firstname.lastname@example.org
10:00 am - 11:00 am GMT
Dr Aideen Ryan is an Associate Professor in Tumour Immunology in the School of Medicine, Discipline of Pharmacology & Therapeutics at NUI Galway. She graduated with a bachelor’s degree in Biochemistry from NUI Galway in 2001 and a PhD in Medicine from the University College Cork in 2006. She completed her postdoctoral training in the labs of Prof. Laurence Egan, and Prof Thomas Ritter at NUI Galway before starting her independent research group at NUI Galway in 2017.
Aideen’s research team are uncovering novel stromal cell targets that shape the immunosuppressive microenvironment in cancer. Aideen’s research is published in high ranking journals and has led to several recent prestigious independent grants, postdoctoral fellowships and international awards including an Top Outstanding Young Peoples Award, Future Leaders Award (SITC, USA), Irish Cancer Society Research Paper of the Year award, NUI Presidents Award for Research excellence, SFI Starting Investigator Research Award.
Aideen is a named inventor on patents relating to discoveries on novel mechanisms to activate the immune system in cancer to enhance immunotherapy. As part of a visiting senior lectureship at Bart’s Cancer Institute, QMUL, London, Aideen’s group are developing 3D models, in collaboration with Prof Fran Balkwill and Dr Daniela Loessner, to investigate mechanisms of immune evasion in colon cancer with particular focus on the influence macrophage/stromal cell interactions on anti-tumour immunity. Her research aims to uncover new stromal cell therapeutic targets to overcome immunosuppression in cancers to optimise and increase response to immunotherapies.
Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.
Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.