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Tertiary lymphoid structures (TLS) are non-encapsulated immune cell aggregates that form at sites of chronic inflammation, including tumors in some cases. Recent studies have shown that the presence of TLS in human tumors is an indicator of positive clinical outcome. However, due to dysregulated angiogenesis, many tumors have poorly organized and leaky vasculature that impedes entry of immune effector cells into tumors and consequently TLS formation. Recently, pre-clinical studies have shown that low doses (well below maximum tolerate dose) of antiangiogenic agents normalize the tumor vasculature, leading us to hypothesize that treating tumors with low doses of these vascular normalizing (VN) therapies will improve immune cell infiltration and TLS formation within the tumor microenvironment (TME).
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