While immunotherapies have shown great promise in treating blood cancers, most clinical trials aimed at treating solid tumors such as pancreatic or lung cancer have failed. Researchers have long thought that solid tumors' resistance to treatment is due to the tumor microenvironment—the cells and matrix that surround solid tumors—but the exact mechanisms behind this blockade were unclear, until now.
create a physical barrier to T cell entry, and these cells also actively suppress T cell function. When the researchers used CAR T cells to target and remove these fibroblasts, rather than targeting the tumor cells themselves, T cells were able to infiltrate and attack the tumor.
The study, which was a collaboration between researchers in the School of Veterinary Medicine, Perelman School of Medicine, and the School of Arts & Sciences, was published in the journalThe researchers say that using a dual approach—by first targeting cancer-associated fibroblasts and then sending in tumor-targeting CAR T cells—could be a therapeutic breakthrough for treatment-resistant solid tumors.
Understanding the stroma's role in blocking anti-tumor immune function is an essential step towards to overcoming this hurdle. To try to pinpoint the mechanisms involved, the team engineered CAR T cells to zero-in and remove cancer-associated fibroblasts, cells within stroma that produce the connective tissue matrix.
They found that removing these cancer-associated fibroblasts effectively broke down the physical barrier surrounding the pancreatic cancer cells so that T cells could infiltrate the tumor.
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