Dendritic Cells: The Unsung Heroes in Tumor Immunity and Immunotherapy

Within the intricate domain of cancer, the immune system assumes a pivotal role in safeguarding the body against the insidious encroachment of tumor cells. Among the array of immune constituents, dendritic cells (DCs) are frequently extolled for their unsung heroism. These remarkable cellular entities play a vital role in orchestrating the immune response against cancer and have garnered considerable attention as promising candidates in the realm of immunotherapy.

Fig 1. DC exosome-mediated antigen presentation and T cell activation (Wang Y, et al. 2020)

What Are Dendritic Cells?

Dendritic cells, a distinct class of immune cells, possess a specialized capability. They are adept at capturing, meticulously processing, and presenting a diverse range of antigens to other immune cells, notably T cells. DCs can be found throughout the body, residing in peripheral tissues, lymph nodes, and various other immune-related organs. Their strategic distribution allows them to sample and process antigens from the environment, thereby contributing to immune surveillance.

Table 1. DC classification (Wang Y, et al. 2020)

Dendritic Cells in Tumor Immunity

When cancer cells initiate uncontrolled proliferation within the human body, their presence often remains inconspicuous to the vigilant immune system. Nonetheless, dendritic cells emerge as the initial responders with a unique capacity to discern and apprehend cancer cell-specific antigens. These vigilant sentinels subsequently embark on a crucial mission, transporting these captured antigens to the lymph nodes, where they present these vital molecular markers to T cells, the linchpin of the immune response.

Dendritic cells play a pivotal role in educating the immune system about the presence of tumor cells. When a DC presents cancer cell antigens to T cells, it triggers an immune response targeted at eliminating the cancerous cells. This process is a crucial step in initiating the body's natural defense mechanisms against cancer.

In addition to their role in antigen presentation, dendritic cells can also secrete various cytokines and chemokines that shape the immune response. By releasing these signaling molecules, DCs can influence the activation of other immune cells, such as cytotoxic T cells and natural killer cells, which are instrumental in the direct killing of cancer cells.

Immunosuppression and Tumor Microenvironment

Despite their critical role in tumor immunity, cancer often employs tactics to evade detection and destruction by dendritic cells and the immune system. Tumor cells can create an immunosuppressive microenvironment that hampers the function of DCs. Factors like the secretion of immune-inhibitory molecules, recruitment of regulatory T cells, and physical barriers in the tumor microenvironment can limit the effectiveness of dendritic cells.

Immunotherapy: Harnessing the Power of Dendritic Cells

Recognizing the vital role of dendritic cells in tumor immunity, researchers have developed strategies to harness the power of these cells for cancer immunotherapy. Dendritic cell-based immunotherapies aim to enhance the body's natural immune response to cancer by exploiting the unique capabilities of DCs.

Dendritic Cell Vaccines

One promising approach involves dendritic cell vaccines. In this therapy, dendritic cells are isolated from a patient's blood, loaded with tumor antigens, and then reinfused into the patient. The reprogrammed dendritic cells present the cancer-specific antigens to T cells, priming them to target the tumor. Dendritic cell vaccines have shown potential in various types of cancer, including melanoma, prostate cancer, and glioblastoma.

Checkpoint Inhibitors

Checkpoint inhibitors are another class of immunotherapies that help unleash the power of dendritic cells. These drugs block immune checkpoints like PD-1 and CTLA-4, which cancer cells often exploit to evade the immune system. By releasing the brakes on the immune system, checkpoint inhibitors enhance the function of dendritic cells and T cells, allowing for a more robust antitumor response.

Chimeric Antigen Receptor (CAR) T Cell Therapy

CAR-T cell therapy is a groundbreaking treatment that involves engineering a patient's T cells to express a chimeric antigen receptor, which enables them to target specific tumor antigens. Dendritic cells can play a vital role in this therapy by assisting in the identification of the most suitable target antigens and optimizing the CAR-T cell therapy's efficacy.

Reference

1. Wang Y, Xiang Y, Xin VW, Wang XW, Peng XC, Liu XQ, Wang D, Li N, Cheng JT, Lyv YN, Cui SZ, Ma Z, Zhang Q, Xin HW. Dendritic cell biology and its role in tumor immunotherapy. J Hematol Oncol. 2020; 13(1):107.