Jayanta Mondal: The loss of Brd7 reawakens dormant breast cancer metastasis initiating cells in the lungs
Jayanta Mondal, Graduate Research Assistant at MD Anderson Cancer Center, shared an article on LinkedIn:
“I am delighted to share that my first-author paper has now been published in Nature Communications (Nature Portfolio).
In this paper, we identify, through an in vivo epigenetic screen, several subunits of the PBAF chromatin remodeling complex as potent enforcers of breast cancer metastatic dormancy. We demonstrate that the loss of Brd7 (a PBAF subunit) reawakens dormant breast cancer metastatis initiating cells in the lung by rewiring the immune-microenvironment and modulating the chromatin architecture.
Subsequently, we found specific therapeutic interventions to counter breast cancer lung metastasis:
- Interestingly, we found an up-regulation of tumor-promoting inflammatory neutrophils and Neutrophil extracellular traps (NETs) formation in the context of breast cancer lung metastasis. Depleting neutrophils or NETs in vivo abrogated breast cancer lung metastasis.
- We, also, implicate CD8+ exhausted T cells and CD4+ stress response T cells in promoting lung metastasis. Utilizing an immunotherapy combination of anti-CTLA4+ anti-LAG3 effectively prevented lung metastasis.
Finally, given that metastasis accounts for >90% of cancer-related deaths, we propose using specific PBAF subunits as a prognostic biomarker to predict breast cancer metastatic relapse. Our study explored the fascinating, yet relatively unexplored, cross-bridge between epigenetics, metastatic reawakening and immune invasion.
This paper is dedicated to the memory of my PhD co-mentor- Filippo G. Giancotti, MD, PhD who was a pioneer in the field of metastasis. Heartfelt thanks to my PhD mentor- Dr. Huse for guiding me through the study, to Junfeng Zhang and to all the co-authors of the paper.
Extremely grateful to all my advisory committee members- Dr. James P.Allison, George Calin, Matthew Gubin, Dr. Behringer.
This collaborative study panned multiple institutions, including MD Anderson Cancer Center and Columbia University Irving Medical Center.”
Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche.
Authors: Jayanta Mondal, et al.
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