VEGFR2 activity on myeloid cells mediates immune suppression in the tumor microenvironment.

Angiogenesis, a hallmark of cancer, is induced by vascular endothelial growth factor-A (hereafter VEGF). As a result, anti-VEGF therapy is commonly used for cancer treatment. Recent studies have found that VEGF expression is also associated with immune suppression in patients with cancer.

Attenuated Microcirculation in Small Metastatic Tumors in Murine Liver.

Metastatic cancer disease is the major cause of death in cancer patients. Because those small secondary tumors are clinically hardly detectable in their early stages, little is known about drug biodistribution and permeation into those metastatic tumors potentially contributing to insufficient clinical success against metastatic disease. Our recent studies indicated that breast cancer liver metastases may have compromised perfusion of intratumoral capillaries hindering the delivery of therapeutics for yet unknown reasons.

Seed- and Soil-Dependent Differences in Murine Breast Tumor Microenvironments Dictate Anti-PD-L1 IgG Delivery and Therapeutic Efficacy.

We sought to determine if Stephen Paget's "seed and soil" hypothesis of organ-preference patterns of cancer metastasis can explain the development of heterogeneity in a tumor microenvironment (TME) as well as immunotherapeutic delivery and efficacy. We established single-cell-derived clones (clones 1 and 16) from parental 4T1 murine breast cancer cells to create orthotopic primary and liver metastasis models to deconvolute polyclonal complexity cancer cells and the difference in TME-derived heterogeneities. Tumor-bearing mice were treated with anti-PD-L1 IgG or a control antibody, and immunofluorescent imaging and quantification were then performed to evaluate the therapeutic efficacy on tumor growth, the delivery of therapy to tumors, the development of blood vessels, the expression of PD-L1, the accumulation of immune cells, and the amount of coagulation inside tumors.

Dissecting the Lymphatic System to Predict Melanoma Metastasis.

Melanoma is the most lethal form of skin cancer in the United States. Current American Joint Committee on Cancer (AJCC) staging uses Breslow depth and ulceration as the two primary tumor factors that predict metastatic risk in cutaneous melanoma. Early disease stages are generally associated with high survival rates.