A recent University of Pennsylvania study has found that getting rid of the barriers surrounding solid tumors allows T cells to kill cancer cells more effectively. The research indicates that it is possible to make immunotherapies more effective at treating solid tumors such as lung cancer and pancreatic cancer.
Immunotherapy is a relatively new type of cancer treatment that involves “training” the immune system to make it more effective at identifying and killing cancerous cells in the body. However, while this treatment has proven to be relatively effective at treating blood cancers, immunotherapies rarely have an impact on solid cancers.
Published in the “Nature Communications” journal, the study represents a major breakthrough in cancer treatment research.
While previous research had shown that stroma, the matrix of fibrous connective tissue and cells that surround solid tumors, could prevent the proliferation of T cells into solid tumors, researchers were not sure how this barrier mechanism worked. Scientists have long theorized that immunotherapy did not work effectively on solid tumors because of specific factors in the tumor microenvironment, but they have been unable to identify exactly why solid tumors do not respond to immunotherapies.
University of Pennsylvania researchers using mouse models may have finally identified the mechanisms that prevent immunotherapies from treating solid tumors such as lung cancer.
The research team comprised of researchers from the Perelman School of Medicine, School of Arts & Sciences and School of Veterinary Medicine. Team members found that cancer-associated fibroblasts, cells in the tumor microenvironment that promote tumor growth, literally erect a physical barrier that prevents killer T cells from reaching tumorous cells. Furthermore, the cancer-associated fibroblasts suppress the immune function of T cells and make them even less effective at killing cancer cells.
School of Veterinary Medicine postdoctoral researcher and physician Zebin Xiao noted that the immunosuppressive environment, coupled with the physical barrier created by the cancer-associate fibroblasts, keeps T cells from entering solid tumors.
After the researchers targeted and removed fibroblasts from tumors in mice, they found that the T cells could enter solid tumors and kill off cancer cells more effectively. In a mouse model of pancreatic cancer, targeting cancer-associated fibroblasts destroyed their barrier function around the pancreatic cancer cells and disrupted the immune suppression function, allowing T cells to infiltrate and attack tumor cells.
According to Xiao, targeting the cancer-associated fibroblasts allowed the researchers to disrupt their barrier function and exhibited a significant anti-tumor effect.
Senior study author Ellen Puré said a dual treatment approach that involves targeting and eliminating cancer-associated fibroblasts followed by CAR T cell treatment could be a breakthrough treatment for hard-to-treat solid tumors.
Given that many more companies such as Renovaro BioSciences Inc. (NASDAQ: RENB) are devoting huge amounts of resources to developing cell and gene therapies for solid tumors, a time could soon come when these types of cancers can also be treated in the same way that blood cancers are treated with immunotherapy.
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