Laszlo Radvanyi

Radvanyi Lab Research Profile:

The focus of our laboratory is on understanding the role of adaptive and innate immunity against cancer, especially during the initial stages of invasive cancer development. We use relevant animal models and human samples for our research. The main goals of our research are:

1. Genomic characterization of early stage breast tumours (pre-invasive to early invasive) and characterization of the changes in early tumour-immune interactions both at the cancer site and systemically;

2. Development of early cancer detection methods and biomarkers of early pre-invasive disease progression towards invasive cancer to inform on possible early detection, prevention, and immunotherapeutic approaches to curtail early human breast cancer progression;

3. Modulation of the innate and adaptive immune system using vaccines and other immunotherapies to determine their effects on early tumour initiation and progression into invasive breast cancer.

It has become evident that early pre-invasive as well as initial invasive cancer lesions shape the quality and direction of the immune response much earlier in the process than we initially thought. This can “imprint” an immune response very early on in a patient that can either inhibit or promote tumour progression. A collection of innate and adaptive immune processes interact to regulate the progression of pre-invasive cancer lesions into invasive cancer. Our goal is to comprehensively characterize these early tumour-immune interactions using multi-omic genomic and immunological tools using both relevant spontaneous rodent cancer models as well as primary human cancer specimens. This will inform on new therapies that can inhibit tumour progression from early stages and trigger memory T-cell responses preventing further tumour dissemination. A powerful model we are developing and using in the lab for this purpose is a spontaneous estrogen-driven breast cancer in the August-Copenhagen-Irish (ACI) rat strain. This tumour model is a solely estrogen-driven model and accurately recapitulates the stages of human hormone receptor (ER+) breast cancer development through specific and temporally defined stages (pre-neoplastic hyperplasias to DCIS to invasive cancer) that can be studied in the laboratory. We will use this model to dissect how the innate immune response regulates early pre-invasive and invasive lesions in the mammary gland and when and how T-cell adaptive responses are activated. For example, we have found that mast cells invade per-tumoural areas early during cancer development and our further clarifying their role. In addition, we have found over-expressed tumour-associated antigens in these early breast cancers and are exploring the possibility of early cancer stage vaccines to prevent further invasive cancer development. Lastly, the ACI rat breast cancer model is useful in developing methods at cancer detection through liquid biopsies, imaging, and other means due to the highly reproducible and step-wise development of cancer over a 5-6 month period of time allowing for different prevention, detection and early treatment approaches to be studied.