Improved Immunotherapy Efficacy by Vascular Modulation

SIMPLE SUMMARY: Although immunotherapy has given the highest rate of improvement in cancer treatment in recent years, there is an urgent need to further improve its efficacy. Numerous strategies aim to transform non-responsive, immunosuppressive tumours into sensitive, immunopermissive tumours. The modulation of the tumour microenvironment, and especially the tumour vasculature offers opportunities for improved sensitivity to immunotherapy. Modulation of tumour blood vessels can enhance tumour oxygenation and T cell infiltration. Additionally, maturation of tumour blood vessels is thought to be involved in the efficient delivery of therapeutic agents. This review compiles the current strategies of vascular modulation to improve the efficacy of different immunotherapies: PD-1/PD-L1 and CTLA-4 antibodies, CAR T cells and cancer vaccines. ABSTRACT: Several strategies have been developed to modulate the tumour vasculature for cancer therapy including anti-angiogenesis and vascular normalisation. Vasculature modulation results in changes to the tumour microenvironment including oxygenation and immune cell infiltration, therefore lending itself to combination with cancer therapy. The development of immunotherapies has led to significant improvements in cancer treatment. Particularly promising are immune checkpoint blockade and CAR T cell therapies, which use antibodies against negative regulators of T cell activation and T cells reprogrammed to better target tumour antigens, respectively. However, while immunotherapy is successful in some patients, including those with advanced or metastatic cancers, only a subset of patients respond. Therefore, better predictors of patient response and methods to overcome resistance warrant investigation. Poor, or periphery-limited, T cell infiltration in the tumour is associated with poor responses to immunotherapy. Given that (1) lymphocyte recruitment requires leucocyte–endothelial cell adhesion and (2) the vasculature controls tumour oxygenation and plays a pivotal role in T cell infiltration and activation, vessel targeting strategies including anti-angiogenesis and vascular normalisation in combination with immunotherapy are providing possible new strategies to enhance therapy. Here, we review the progress of vessel modulation in enhancing immunotherapy efficacy.