Innate immune cells for immunotherapy of autoimmune and cancer disorders

Abstract

Modulation of the immune system has been widely targeted for the treatment of several immune-related diseases, such as autoimmune disorders and cancer, due to its crucial role in these pathologies. Current available therapies focus mainly on symptomatic treatment and are often associated with undesirable secondary effects. For several years, remission of disease and subsequently recovery of immune homeostasis has been a major goal for immunotherapy. Most current immunotherapeutic strategies are aimed to inhibit or potentiate directly the adaptive immune response by modulating antibody production and B cell memory, as well as the effector potential and memory of T cells. Although these immunomodulatory approaches have shown some success in the clinic with promising therapeutic potential, they have some limitations related to their effectiveness in disease models and clinical trials, as well as elevated costs. In the recent years, a renewed interest has emerged on targeting innate immune cells for immunotherapy, due to their high plasticity and ability to exert a potent and extremely rapid response, which can influence the outcome of the adaptive immune response. In this review, we discuss the immunomodulatory potential of several innate immune cells, as well as they use for immunotherapy, especially in autoimmunity and cancer.

Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice

“…The pathogenic role of DCs has been evaluated in several autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and SLE . In fact, DCs from SLE patients display an increased expression of maturation markers (CD86/CD80) indicating an inflammatory profile in comparison to healthy donors . Interestingly, a tolerogenic phenotype can be successfully induced in DCs from patients by pharmacological modulation with Dexa and Rgz .…”

“…7,32 In fact, DCs from SLE patients display an increased expression of maturation markers (CD86/ CD80) indicating an inflammatory profile in comparison to healthy donors. 2,32 Interestingly, a tolerogenic phenotype can be successfully induced in DCs from patients by pharmacological modulation with Dexa and Rgz. 3 Tolerogenic DCs with similar properties have been loaded with autoantigens and employed in randomized clinical trials to induce tolerance in multiple sclerosis, rheumatoid arthritis and type I diabetes patients.…”

“…Dendritic cells (DCs) are specialized antigen‐presenting cells that play a central role in determining the induction of immunity or tolerance. Notably, the tolerogenic function of DCs has gained interest in recent years . Tolerogenic dendritic cells (tolDCs) are characterized by reduced expression of co‐stimulatory molecules, the up‐regulation of inhibitory molecules and increased production of anti‐inflammatory cytokines .…”

“…Notably, the tolerogenic function of DCs has gained interest in recent years. 1,2 Tolerogenic dendritic cells (tolDCs) are characterized by reduced expression of co-stimulatory molecules, the upregulation of inhibitory molecules and increased production of anti-inflammatory cytokines. 1 A stable tolDC phenotype can be genetic and pharmacologically generated in vitro by treatments that block or prevent DC maturation.…”

Innate Immune Cells and Their Contribution to T-Cell-Based Immunotherapy

“…Macrophages are multifunctional components of the innate immunity and consist of different subgroups with different maturation stages and tissue localization [40]. They are the primary defense against pathogens where they exploit their function through phagocytosis and the production of inflammatory cytokines [76].…”