The current role of dendritic cells in the progression and treatment of colorectal cancer

Abstract

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Dendritic cells (DCs) constitute a heterogeneous group of antigen-presenting cells that are important for initiating and regulating both innate and adaptive immune responses. As a crucial component of the immune system, DCs have a pivotal role in the pathogenesis and clinical treatment of CRC. DCs cross-present tumor-related antigens to activate T cells and trigger an antitumor immune response. However, the antitumor immune function of DCs is impaired and immune tolerance is promoted due to the presence of the tumor microenvironment. This review systematically elucidates the specific characteristics and functions of different DC subsets, as well as the role that DCs play in the immune response and tolerance within the CRC microenvironment. Moreover, how DCs contribute to the progression of CRC and potential therapies to enhance antitumor immunity on the basis of existing data are also discussed, which will provide new perspectives and approaches for immunotherapy in patients with CRC.

Keywords: Colorectal cancer; dendritic cells; treatment strategies; tumor progression.

Figure 1

DC classification. Origin of dendritic cells (DCs) and the expression of specific surface markers on each subset of DCs. Human myeloid cells originate from hematopoietic stem cells (HSCs) and differentiate into granulocyte–macrophage DC progenitors (MDPs), common DC progenitors (CDPs), common monocyte progenitors (cMoPs), and common lymphoid progenitors (CLPs). CDPs and CMoPs differentiate into pre-conventional DCs (pre-pDCs) and monocytes, respectively, while pre-plasmacytoid DCs (pre-pDCs) are differentiated from CDPs. LCs originate from embryonic progenitors. Pre-pDCs further differentiate into cDC1s and cDC2s, while pre-pDCs and CLPs co-differentiate into plasmacytoid DCs (pDCs). Transitional DCs (tDCs) are derived from pDCs and cDC2s.

Figure 2

Summary of the mechanisms by which DCs influence CRC progression. I. Antitumor mechanisms: When the body finds the presence of CRC tumor antigens, DCs are rapidly activated, present CRC antigens to MHC molecules, and sense damage signals in the TME through special receptors, such as pattern recognition receptors, to induce antitumor adaptive CD8⁺ and CD4⁺ T-cell responses. Mature DCs are translocated from the TME to the TDLN along a chemokine gradient, priming naive T cells and attracting T cells and other immune cells. II. Tumor-promoting mechanisms: a. After DC differentiation is blocked, an obvious immunosuppressive cytokine spectrum is formed that inhibits the activation and proliferation of T cells and weakens the immune attack on colorectal cancer cells to induce immune tolerance; b. Impaired DC differentiation promotes the accumulation of other cell subsets with immunosuppressive functions, such as MDSCs, inducing the development of Tregs, hindering DC maturation, and promoting tumor progression; c. Immunosuppressive regulation of DCs induces proliferation of Treg lymphocytes and autoreactive T cells, thereby promoting immune tolerance.