We found that elevated ICAM-1 expression in breast cancer cells results in a favorable outcome and prolonged survival of breast cancer patients. Notably, the presence of ICAM-1 on E did not alter tumor growth or the leukocyte composition in the tumor microenvironment.
Interestingly, the elimination of Tregs led to the rapid killing of primary tumor cells independently of tumor ICAM-1 expression. The whole lung imaging of these cells by light sheet microscopy LSM revealed that both Wild type WT - and ICAMdeficient E cells were equally disseminated from resected tumors and accumulated inside the lung vasculature at similar magnitudes.
ICAMdeficient breast cancer cells developed, however, much larger metastatic lesions than their control counterparts. Strikingly, the vast majority of these cells gave rise to intravascular tumor colonies both in spontaneous and experimental metastasis models.
In the latter model, ICAM-1 expressing E but not their ICAMdeficient counterparts were highly susceptible to elimination by neutrophils adoptively transferred from E tumor-bearing donor mice. Ex vivo , neutrophils derived from tumor-bearing mice also killed cultured E cells via ICAMdependent interactions. Collectively, our results are a first indication that ICAM-1 expressed by metastatic breast cancer cells that expand inside the lung vasculature is involved in innate rather than in adaptive cancer cell killing.
This is also a first indication that the breast tumor expression of ICAM-1 is not required for CTL-mediated killing but can function as a suppressor of intravascular breast cancer metastasis to lungs. ICAM-1, also known as CD54, is a cell surface glycoprotein that is expressed primarily on endothelial cells and the cells of the immune system 1 , 2.
