IBCN 2020: Tumor Immune Microenvironment in Response to Radiotherapy Versus BCG in a Murine Model of Bladder Cancer

(UroToday.com) Several virtual posters presented at the Translational Track session added to the growing body of evidence that tumor microenvironment influences the behavior of bladder cancer and can impact response to therapies.


Kara Lombardo, BSc, discussed findings from investigators at Johns Hopkins and Columbia University who compared changes in local tumor immune microenvironment in response to radiotherapy versus BCG in a murine bladder cancer model. Mice exposed to carcinogen subsequently received radiotherapy or intravesical BCG instillation, and were compared with controls. They noted no tumors in carcinogen-exposed mice treated with BCG, when compared with controls and those treated by radiotherapy. mRNA and protein analysis indicated that intravesical BCG instillation resulted in increased expression of STimulator of INterferon Genes (STING), which was consistent with elevated levels of several downstream cytokines and chemokines.

The investigators concluded that BCG instillation causes a robust pro-inflammatory immune response compared to radiation in murine bladder cancer models, possibly via STING-dependent induction of cytokines and chemokines (Figure). They also note that elevated levels of Trex1 may inhibit STING activation and cytokine response in radiated samples. Given that the role of radiotherapy combined with immunotherapy is currently being investigated in patients with non-muscle invasive bladder cancer, these findings highlight the need to uncover mechanisms of radiation-induced immune response in this disease to optimally combine both treatment modalities.

Figure: Proposed immunomodulatory mechanisms for radiation and BCG in a murine bladder cancer model.

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Next planned steps include assessing different fractionated doses of radiotherapy and their associated responses.

Presented by: Kara Lombardo, BSc, Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Written by: Anirban P. Mitra, MD, PhD, Urologic Oncology Fellow, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Twitter: @APMitra, with Ashish M. Kamat, MD, MBBS, President of IBCN and IBCG, Endowed Professor, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Twitter: @UroDocAsh at the International Bladder Cancer Network (IBCN) Annual Meeting, #IBCN2020, October 17, 2020.
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