AACR-Triple Negative Breast Cancer Foundation Research Fellowship
The AACR-Triple Negative Breast Cancer Foundation Research Fellowship represents a joint effort to encourage and support postdoctoral or clinical research fellows to conduct triple negative breast cancer research and to establish a successful career path in this field. Funded research can be basic, translational, clinical, or epidemiological in nature.
Progress in the triple negative breast cancer (TNBC) research field is hampered by the use of pre-clinical models that use a single inbred genetic background. Dr. Sipe has developed a novel murine model by crossing an established TNBC strain into the background of the largest genetic reference population. This approach will allow Dr. Sipe to interrogate TNBC phenotypes across a diverse and well characterized genetic background. Much like patients, this “humanized” pre-clinical model has differing severity of TNBC phenotypes.
Dr. Sipe earned her PhD from the University of Virginia where she demonstrated critical effects of sympathetic innervation of adipose tissue. To integrate her expertise in physiology and metabolism with the tumor microenvironment, Dr. Sipe joined the University of Tennessee Health Science Center to study obesity and breast cancer. Dr. Sipe is set to examine genetic determinants of TNBC using a unique murine genetic reference population.
Acknowledgement of Support
I am honored to accept this 2020 AACR-Triple Negative Breast Cancer Foundation Research Fellowship and complete the proposed work to generate a “humanized” model of TNBC. At the culmination of this proposal, we will identify novel genes that impact TNBC severity, spearheading new avenues of independent research and ultimately improving TNBC outcomes.
An outstanding challenge in the cancer immunotherapy field is to devise strategies to vaccinate the majority of triple-negative breast cancer (TNBC) patients who do not respond to immune-checkpoint blockade against their own individual tumor. Local tumor radiotherapy (RT) represents a promising partner for immunotherapy due to its ability to convert the tumor into an in situ vaccine by enhancing both, tumor antigens expression and release, and the production by irradiated cancer cells of inflammatory signals activating dendritic cells. However, multiple barriers exist in the tumor that preclude efficient in situ vaccination by RT, such as the upregulation of the “don’t-eat-me” signal provided by the CD47-SIRPα pathway. Indeed, CD47 expression correlates with poor-prognosis molecular subtypes, such as TNBC. Thus, Dr Lhuillier has been determining the effects of RT combined with SIRPα blockade on phagocytic cells functions and on the development of anti-tumor immunity and abscopal responses in vivo using a TNBC mouse model.
Dr. Lhuillier obtained her bachelor’s degree in biology from the University of Nantes (France) in 2010 and her master’s degree in immunology in 2012 from the University Pierre and Marie Curie, Paris. She then joined the Gustave Roussy Institute and completed her PhD in 2016. Seeking to pursue a career in the cancer immunotherapy field, she has been pursuing postdoctoral training at Weill Cornell Medicine. Her current work focuses on exploring how to use radiation therapy as an adjuvant to generate an in situ vaccine for the treatment of breast cancers refractory to immune-checkpoint blockade.
Acknowledgement of Support
Receiving the AACR-TNBC Foundation Research Fellowship is a great honor and represents an excellent opportunity to achieve my research goals hoping that my work will advance our understanding of the mechanisms driving breast cancer resistance to treatment and provide the rationale for clinical translation of this novel approach in patients.