From Tumor Immunosuppression to Eradication: Targeting Homing and Activity of Immune Effector Cells to Tumors

Abstract

Unraveling the mechanisms used by the immune system to fight cancer development is one of the most ambitious undertakings in immunology. Detailed knowledge regarding the mechanisms of induction of tolerance and immunosuppression within the tumor microenvironment will contribute to the development of highly effective tumor eradication strategies. Research within the last few decades has shed more light on the matter. This paper aims to give an overview on the current knowledge of the main tolerance and immunosuppression mechanisms elicited within the tumor microenvironment, with the focus on development of effective immunotherapeutic strategies to improve homing and activity of immune effector cells to tumors.

Effects of dexmedetomidine on patients undergoing radical gastrectomy

“…Cancer patients usually present with immunosuppression [33,34]. Host immunosuppression influences anti-tumor immune responses.…”

Hypoxia and acidosis: immune suppressors and therapeutic targets

“…‘Alternatively activated’ M2 macrophages express immunosuppressive ligands . During tumour progression, neoplastic cells evade immune surveillance by evolving mechanisms that subvert the normal tumour‐specific immune response, such as distorting the macrophage populations to favour the M2 phenotype or overexpression of checkpoint ligands . Up‐regulated expression of immunosuppressive ligands, such as B7H4, on both tumour‐associated macrophages (TAMs) and tumour cells are also found in the tumour‐microenvironment .…”

“…Myeloid‐derived suppressor cells (MDSCs) are another type of immune suppressors in the tumour microenvironment that have known negative effects on T‐cell and NK cell functions . This inhibition of immune surveillance via alternative activation of immune cells is mediated by ligand expression and cytokines, as well as soluble and physico‐chemical factors of the tumour microenvironment . Herein, we consider tumour hypoxia and acidity as two important physico‐chemical factors that can inhibit anti‐tumour immune responses (Fig.…”

Antigen-Specific Antitumor Responses Induced by OX40 Agonist Are Enhanced by the IDO Inhibitor Indoximod

“…In addition to augmenting the effector arm of the immune system, extensive studies have been devoted to immune tolerance and tumor-mediated immunosuppressive mechanisms, which render effector T cells ineffective in clearing malignant cells (24)(25)(26). Tumor-mediated immune suppression includes inhibitory mechanisms elicited by tumor cells directly (coinhibitory receptor/ligand interactions, secretion of inhibitory cytokines and other molecules) or indirectly (mechanisms based on tumorrecruited suppressive immune cells).…”