Jing Hu, PhD
Jing Hu, PhD
Memorial Sloan Kettering Cancer Center
Metastasis is a major clinical hurdle in breast cancer treatment, with poor prognosis (5-year survival around 26.5%). Despite surgical resection of the primary tumor and systemic therapy to suppress residual disease, distant metastatic relapse may still occur within a few months to years, implying the existence of latent metastatic cells that may last for decades in the distant organs without being detected in clinic. They eventually generate overt metastasis, which is highly resistant to current therapies. Therefore, the predominant concern in the clinic is about how to prevent or treat metastatic relapse by cancer cells that had already disseminated in the distant organs at the time of diagnosis. We recently identified that NK cells suppress outgrowth of disseminated breast cancer cells. However, emergence of immune evasive clones eventually triggers aggressive outbreak. The mechanisms underlying immune evasion of metastatic outbreak are largely unknown.
We discovered that breast cancer cells contain cytosolic double-stranded DNA (dsDNA), likely as a result of genomic instability. The stimulator of interferon genes (STING) pathway, triggered by cytosolic dsDNAs, is critical for initiating immune defense against pathogens. Preliminary data suggests that cancer intrinsic STING signal is reduced in immune-evasive metastatic outbreak and restoration of STING activity suppresses metastasis, possibly through immune responses. Therefore, we hypothesize that aggressive metastatic cells inhibit STING signal to evade immune surveillance.
As a Terri Brodeur Fellow, Dr. Hu will apply comprehensive approaches to elucidate the mechanisms for STING-mediated metastasis suppression, to dissect determinants that inhibit STING activity during metastatic progression, and to preclinically test potential therapeurtic targets that suppress metastatic outgrowth. Completion of the work will enrich the knowledge of immune responses in the metastatic microenvironment and contribute innovative ideas for treating metastatic relapse of breast cancer.
Dr. Jing Hu obtained her Ph.D. in Molecular Cancer Biology Program at Duke University, under the supervision of Dr. Xiao-Fan Wang. During her Ph.D., Dr. Hu has discovered microRNA-mediated signal networks that regulate the biological properties of glioma-initiating cells (GICs) and their adaptation to the hypoxic tumor microenvironment. Dr. Hu is currently a post-doctoral fellow at Memorial Sloan Kettering Cancer Center in the lab of Dr. Joan Massagué.