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.

Programme:

• 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

Episode summary:

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

Published papers:

https://pubmed.ncbi.nlm.nih.gov/30228206/

https://www.biorxiv.org/content/10.1101/2021.06.18.447879v1

References

1. 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
2. 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 kristine.lennie@researcher-app.com