Dendritic cell vaccines improve the glioma microenvironment: Influence, challenges, and future directions

Abstract

Introduction Gliomas, especially the glioblastomas, are one of the most aggressive intracranial tumors with poor prognosis. This might be explained by the heterogeneity of tumor cells and the inhibitory immunological microenvironment. Dendritic cells (DCs), as the most potent in vivo functional antigen‐presenting cells, link innate immunity with adaptive immunity. However, their function is suppressed in gliomas. Therefore, overcoming the dysfunction of DCs in the TME might be critical to treat gliomas. Method In this paper we proposed the specificity of the glioma microenvironment, analyzed the pathways leading to the dysfunction of DCs in tumor microenvironment of patients with glioma, summarized influence of DC‐based immunotherapy on the tumor microenvironment and proposed new development directions and possible challenges of DC vaccines. Result DC vaccines can improve the immunosuppressive microenvironment of glioma patients. It will bring good treatment prospects to patients. We also proposed new development directions and possible challenges of DC vaccines, thus providing an integrated understanding of efficacy on DC vaccines for glioma treatment.

M2 macrophage marker CHI3L2 could serve as a potential prognostic and immunological biomarker in glioma by integrated single‐cell and bulk RNA‐Seq analysis

“…27,28 Many of the cytokines involved in the pathogenesis of Tumor microenvironment and immune cell infiltration have gradually been regarded as hotspots in glioma and they could be used to predict patents' prognosis or immune responses. 29,30 Wang et al revealed the immunosuppressive microenvironment roles of Podoplanin (PDPN) in glioma with IDH wildtype. 31 Zhang et al successfully established a tryptophan metabolism-based model in glioma to predict these patients' prognosis and immune responses.…”

“…Tumor microenvironment and immune cell infiltration have gradually been regarded as hotspots in glioma and they could be used to predict patents’ prognosis or immune responses 29,30 . Wang et al revealed the immunosuppressive microenvironment roles of Podoplanin (PDPN) in glioma with IDH wildtype 31 .…”

Immunotherapy in glioblastoma treatment: Current state and future prospects

“…Thus, they are extremely important for the induction of acquired immunity, also influencing the lymphocytic response, its differentiation, and antigen presentation. With this in mind, within GBM pictures, DCs are found with reduced function, being in an inhibited or immature state, which can be related to the severe tumor microenvironment, DCs are kept with low function due to the inhibitory effect of the immune microenvironment, and this status is problematic for body function, but reversed by DC vaccines[ 147 ]. This is due to the fact that the advantages of DCs vaccines are based on in vitro matured dendritic cells, usually from the affected individual himself, which can activate previously inhibited Ts lymphocytes, increasing the patient's adaptive response, increasing the expression of MHCs, cytokines and chemokines, and promoting an intense migration of immune cells to the immunosuppressive microenvironment found in GBM[ 147 ].…”

Overcoming Suppressive Tumor Microenvironment by Vaccines in Solid Tumor

“…The whole tumor lysates contain a variety of tumor antigens, such as TSAs. However, other unrelated antigens are also present in the tumor lysates, resulting in decreased specificity that hinders antigens processing and presentation of DCs [ 21 ]. Peptide- or protein-based DC vaccines can reduce the incidence of autoimmune-related adverse reactions while maintaining tumor selectivity [ 17 ].…”