Ashish Kulkarni, an assistant professor in the Chemical Engineering Department (ChE) at the University of Massachusetts Amherst and head of the Kulkarni Research Group there, is the lead author of a paper published online on July 2 in Nature Biomedical Engineering, a high-impact engineering journal in the prestigious Nature Group. The newly published paper describes pioneering research on some of the body’s natural immune cells called macrophages, which cancer cells routinely subvert and enlist to suppress the body’s immune response to cancer. This subverted function is called immunosuppression, and macrophages act as one of the key players. But, in this trailblazing study, the researchers have been able to “re-educate” these immunosuppressive macrophages to act aggressively against tumors and eat cancer cells.
Macrophages normally form one of the first lines of defense in our innate immune system. However, under the influence of cancer cells, macrophages are often recruited to do cancer’s bidding, thereby creating an environment that acts in reverse, to suppress the immune system in the face of encroaching cancer.
“Tumors grow by creating an immunosuppressive microenvironment,” Kulkarni explains. “Cancer does that by exploiting several mechanisms, one of which is recruitment of immune-suppressive cells such as macrophages.” He says that, when this happens, macrophages can also help the tumors spread to other parts of the body.
As Kulkarni says about this groundbreaking research, “We have engineered a self-assembled nanomaterial that can re-educate the macrophages to be anti-tumorigenic and additionally enhance [their] ability to eat the cancer cells efficiently.”
Kulkarni notes that, in laboratory studies, a lower dose of this dual-functional therapy was more effective in halting the growth as well as spread of two aggressive tumors in animal models than the current macrophage-targeted therapies.
“This approach could be used as an immunotherapy to re-educate the macrophages in different cancers and could be combined with other immunotherapies such as immune checkpoint inhibitors,” as Kulkarni concludes.
Kulkarni’s research group is an interdisciplinary team working at the interface of engineering and immunology to address challenges in clinics. “Our mission is to treat diseases and improve human health by engineering new approaches for both fundamental understanding of the disease progression and efficient therapeutic modulation of the immune system,” as Kulkarni says.
As the Nature Biomedical Engineering paper observes, “Effectively activating macrophages that can ‘eat’ cancer cells is challenging. In particular, cancer cells secrete macrophage colony stimulating factor (MCSF), which polarizes tumor-associated macrophages from an antitumor M1 phenotype to a pro-tumorigenic M2 phenotype. Also, cancer cells can express CD47, a ‘don’t eat me’ signal that ligates with the signal regulatory protein alpha (SIRPα) receptor on macrophages to prevent phagocytosis.”
But the innovative research described in the new Nature Biomedical Engineering paper “can disable both mechanisms,” as the researchers conclude.
In addition to the ChE department at UMass, the following institutions were involved in the research described in the Nature Biomedical Engineering paper: Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston; Center for Bioactive Delivery, Institute for Applied Life Sciences, UMass Amherst; India Innovation Research Center, Invictus Oncology, New Delhi, India; Dana Farber Cancer Institute, Boston; Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts. (July 2018)