Blood Pressure Drug Could Help to Thwart Lymph Node Tumors’ Evasive Tactics
Research by scientists at Massachusetts General Hospital (MGH) and Boston University School of Medicine may help to explain why cancer cells that spread to lymph nodes (LN) can resist attack by immune cells. Their studies found that an increased physical force—known as solid stress—in metastatic lymph nodes effectively disrupts the ability of immune system cells to infiltrate the lymph node tumors and fight the cancer cells. The team’s experiments in mice showed that relieving solid stress led to a 15-fold increase in the presence of lymphocytes in lymph-node metastases.
Additional laboratory studies also showed that the antihypertensive drug losartan can act to relieve some of the effects of solid stress and so allow increased numbers of lymphocytes to infiltrate metastatic lesions. “We know that lymph nodes are often the first place cancer spreads as it progresses, said Timothy P. Padera, PhD, an investigator in radiation oncology at MGH and a 2021–2026 MGH research scholar.
“We also know that our immune system can attack and kill cancer cells. One of the perplexing questions that has been at the core of the recent work in my lab is how can organs that generate our immune responses—lymph nodes—permit cancer cells to survive and take them over instead of attacking them? This was the driving motivation behind this study.”
Padera is co-corresponding author of the team’s paper in Nature Biomedical Engineering, in which the team concluded, “Solid-stress-mediated impairment of lymphocyte infiltration into lymph-node metastases suggests a therapeutic route for overcoming T-cell exclusion during immunotherapy … Our data suggest that controlling solid stresses in LNs may enhance anticancer immunity by improving T-cell trafficking into LN metastases.” The paper is titled, “Solid stress impairs lymphocyte infiltration into lymph-node metastases.”