Tumor-Infiltrating Dendritic Cells: Decisive Roles in Cancer Immunosurveillance, Immunoediting, and Tumor T Cell Tolerance

Abstract

The tumor microenvironment plays a key role in progression of tumorigenesis, tumor progression, and metastasis. Accumulating data reveal that dendritic cells (DCs) appear to play a key role in the development and progression of metastatic neoplasia by driving immune system dysfunction and establishing immunosuppression, which is vital for tumor evasion of host immune response. Consequently, in this review, we will discuss the function of tumor-infiltrating DCs in immune cell signaling pathways that lead to treatment resistance, tumor recurrence, and immunosuppression. We will also review DC metabolism, differentiation, and plasticity, which are essential for metastasis and the development of lung tumors. Furthermore, we will take into account the interaction between myeloid cells and DCs in tumor-related immunosuppression. We will specifically look into the molecular immune-related mechanisms in the tumor microenvironment that result in reduced drug sensitivity and tumor relapse, as well as methods for combating drug resistance and focusing on immunosuppressive tumor networks. DCs play a crucial role in modulating the immune response. Especially, as cancer progresses, DCs may switch from playing an immunostimulatory to an inhibitory role. This article’s main emphasis is on tumor-infiltrating DCs. We address how they affect tumor growth and expansion, and we highlight innovative approaches for therapeutic modulation of these immunosuppressive DCs which is necessary for future personalized therapeutic approaches.

Erythrocyte membrane-camouflaged DNA-functionalized upconversion nanoparticles for tumor-targeted chemotherapy and immunotherapy

“…Mature DCs play a pivotal role in engulfing and presenting antigens from dying tumor cells to T lymphocytes, thus promoting intratumoral infiltration of CD8 + CTLs. 69 Immunosuppressive Tregs are often enriched in the tumor to protect tumor cells from attack by the immune system. 70 As shown in Fig.…”

Low expression of lysosome-related genes KCNE1, NPC2, and SFTPD promote cancer cell proliferation and tumor associated M2 macrophage polarization in lung adenocarcinoma

“…Several cytokines exhibiting direct effector roles and the ability to activate other immune cells (including B cells, DCs, and CD8 + T cells) are secreted by CD4 + T cells [ 31 , 32 ]. The immune response in lung cancer relies heavily on tumor-infiltrating CD4 + T cells [ 33 , 34 ]. One way in which CD4 + T cells influence tumors is by facilitating the entry of CD8 + T cells into the tumor site and the infected mucosa; CD4 + T cells are also necessary for the inhibition of angiogenesis at the tumor site [ 35 ].…”

Metal-Based Nanoparticles for Cancer Metalloimmunotherapy

“…These signals can be recognized by pattern recognition receptors (PRR), including Toll-like receptors (TLRs), retinoic acid-inducible gene I-like receptors (RLRs), NOD-like receptors (NLRs), and stimulator of interferon genes (STING) [ 22 ]. Upon maturation, DCs and macrophages exhibit an elevated expression of MHC molecules and costimulatory molecules (B7-1/B7-2) for the priming of T cells, and they secrete cytokines and chemokines that further activate T cells and enhance their migration to peripheral lymphoid organs or to the target site [ 24 , 25 ].…”