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Improvement of patient survival by anti-angiogenic therapy has proven limited. A vaccination approach inducing an immune response against the tumor vasculature combines the benefits of immunotherapy and anti-angiogenesis, and may overcome the limitations of current anti-angiogenic drugs. Strategies to use whole endothelial cell vaccines and DNA- or protein vaccines against key players in the VEGF signaling axis, as well as specific markers of tumor endothelial cells, have been tested in preclinical studies. Current clinical trials are now testing the promise of this specific anti-cancer vaccination approach. This review will highlight the state-of-the-art in this exciting field of cancer research. [ABSTRACT FROM AUTHOR]

Glioma-associated microglia and macrophages (GAMs) and myeloid-derived suppressor cells (MDSCs) condition the glioma microenvironment to generate an immunosuppressed niche for tumour expansion. This immunosuppressive microenvironment is considered to be shaped through a complex multi-step interactive process between glioma cells, GAMs and MDSCs. Glioma cells recruit GAMs and MDSCs to the tumour site and block their maturation. Glioma cell-derived factors subsequently skew these cells towards an immunosuppressive, tumour-promoting phenotype. Finally, GAMs and MDSCs enhance immune suppression in the glioma microenvironment and promote glioma growth, invasiveness, and neovascularization. The local and distant cross-talk between glioma cells and GAMs and MDSCs is regulated by a plethora of soluble proteins and cell surface-bound factors, and possibly via extracellular vesicles and platelets. Importantly, GAMs and MDSCs have been reported to impair the efficacy of glioma therapy, in particular immunotherapeutic approaches. Therefore, advancing our understanding of the function of GAMs and MDSCs in brain tumours and targeted intervention of their immunosuppressive function may benefit the treatment of glioma. [ABSTRACT FROM AUTHOR]

Chemotherapy (CT), radiotherapy (RT), and chemoradiotherapy (CRT) are able to alter the composition of the tumor immune microenvironment (TIME). Understanding the effect of these modalities on the TIME could aid in the development of improved treatment strategies. Our aim was to systematically review studies investigating the influence of CT, RT or CRT on different TIME markers. The EMBASE (Ovid) and PubMed databases were searched until January 2019 for prospective or retrospective studies investigating the dynamics of the local TIME in cancer patients (pts) treated with CT, RT or CRT, with or without targeted agents. Studies could either compare baseline and follow-up specimens - before and after treatment - or a treated versus an untreated cohort. Studies were included if they used immunohistochemistry and/or flow cytometry to assess the TIME. In total we included 110 studies (n = 8850 pts), of which n = 89 (n = 6295 pts) compared pre-treatment to post-treatment specimens and n = 25 (n = 2555 pts) a treated versus an untreated cohort (4 studies conducted both comparisons). For several tumor types (among others; breast, cervical, esophageal, ovarian, rectal, lung mesothelioma and pancreatic cancer) remodeling of the TIME was observed, leading to a potentially more immunologically active microenvironment, including one or more of the following: an increase in CD3 or CD8 lymphocytes, a decrease in FOXP3 Tregs and increased PD-L1 expression. Both CT and CRT were able to immunologically alter the TIME. The TIME of several tumor types is significantly altered after conventional therapy creating opportunities for concurrent or sequential immunotherapy. [ABSTRACT FROM AUTHOR]