Using macrophage activation to augment immunotherapy of established tumours

摘要: Successful immunotherapy will require alteration of the tumour microenvironment and/or decreased immune suppression. Tumour-associated macrophages (TAMs) are one major factor affecting microenvironment. We hypothesised that altering TAM phenotype would augment efficacy immunotherapy. and others have reported 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA, Vadimezan) has ability to change phenotypes, inducing a conducive antitumour responses. therefore combined DMXAA with active immunotherapies, evaluated anti-tumour efficacy, cell phenotypes (flow cytometry), (RT–PCR). In several different murine models for lung cancer, DMXAA-induced macrophage activation significantly augmented therapeutic effects By increasing influx neutrophils (M1) tumour, altered myeloid thus changing intratumoural M2/non-M2 immunoinhibitory ratio. It also be more pro-inflammatory. Modulating during resulted in increased numbers, activity, antigen-specificity CD8+ T cells. Macrophage depletion reduced effect combining activation, supporting importance TAMs effect. dramatically Our observations suggest addition agents activate should considered future trials.