In a recent review published in the journal Immunity, researchers delved into the role of dendritic cells (DCs) in mediating T-cell responses in cancer. The review focused on the interactions between DCs and T cells, both at the initial priming stage and in the tumor microenvironment. The authors explored the implications of these interactions for innovative cancer immunotherapies.
DCs, discovered approximately 50 years ago, serve as the guardians of the immune system. They assess tissue conditions and process antigens to determine potential dangers. DCs can modulate T-cell responses based on the signals they receive, either fostering tolerance or triggering immune responses.
Recent studies have revealed multiple subsets and states of DCs. The primary focus has been on classical or conventional Type 1 DCs (cDC1s) and conventional Type 2 DCs (cDC2s) found in secondary lymphoid organs and tumors. However, monocyte-derived DCs (MoDCs) and interferon-producing cells (IPCs), or plasmacytoid DCs (pDCs), are also significant players. Each subset has its own origins and functions.
DCs can adopt different activated states once they reach the tumor microenvironment. Factors affecting DC migration include inflammation, chemokine receptors, and interactions with other immune cells. In non-lymphoid tissues, DCs employ scavenger receptors for antigen sampling. One particular receptor, C-Type Lectin Domain Family 9 Member A (CLEC9A), stands out for its potential in enhancing antigen presentation to CD8+ T cells.
DCs respond to various cues, such as pathogen-associated and damage-associated molecular patterns, as well as inflammatory cytokines. These cues can prompt migration or enhance antigen presentation by DCs. Interestingly, the programs for T-cell activation and migration seem to be controlled separately.
Migratory DCs, upon reaching the lymph nodes, interact with naive CD4+ and CD8+ T cells by presenting specific peptide-MHC complexes. These interactions initiate a series of signals that lead to a fully active T-cell response. In the tumor microenvironment, different DC subsets influence the fate and response of T cells. Understanding the function and interaction of these cells in tumors can provide crucial insights for developing effective cancer treatments.
Genomic and transcriptomic studies have revealed immune cell patterns related to tumor genotypes, particularly involving DCs and T cells. Some oncogenic mutations appear to suppress DC infiltration, leading to immune cold tumor microenvironments that contribute to immunotherapy resistance. Factors produced within the tumor microenvironment, such as Interleukin-10 (IL-10), Interleukin-6 (IL-6), and Vascular Endothelial Growth Factor (VEGF), further suppress DC responses and promote tumor growth. Targeting DC function could have potential therapeutic implications.
Efforts have been made to harness the power of DCs for cancer therapies. Current therapeutic aspirations include increasing DC abundance in tumors and lymph nodes and enhancing their immunogenic functions. Although past DC-based vaccination strategies have yielded mixed results, next-generation vaccines aim for improved outcomes.
Overall, the review emphasizes the crucial role of DCs in cancer immunity and highlights their potential as therapeutic targets for innovative cancer immunotherapies.