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Simple Summary: Cancer stands as the second leading cause of death globally. Over the years, concerted efforts have been devoted to developing innovative and effective therapies for tumor eradication and to prevent recurrence. A critical factor contributing to therapy failures is the patient's immune response. Consequently, recent endeavors, such as immune checkpoint blockade, adoptive cell therapy, monoclonal antibodies, and cancer vaccines, aim to enhance a patient's immune system, maximizing the benefits of therapies for tumor clearance and subsequent memory formation. Dendritic cells (DCs) play a pivotal role in regulating the immune response. DCs are a heterogeneous population with varying functions in the tumor microenvironment. Reprogramming tumor-infiltrating DCs can dramatically improve the immune response against tumors and has shown significant therapeutic potential in pre-clinical models. In this review, we summarize the subsets and functions of dendritic cells and their role in shaping the anti-tumor T cell immune response. Among professional antigen-presenting cells, dendritic cells (DCs) orchestrate innate and adaptive immunity and play a pivotal role in anti-tumor immunity. DCs are a heterogeneous population with varying functions in the tumor microenvironment (TME). Tumor-associated DCs differentiate developmentally and functionally into three main subsets: conventional DCs (cDCs), plasmacytoid DCs (pDCs), and monocyte-derived DCs (MoDCs). There are two major subsets of cDCs in TME, cDC1 and cDC2. cDC1 is critical for cross-presenting tumor antigens to activate cytotoxic CD8+ T cells and is also required for priming earlier CD4+ T cells in certain solid tumors. cDC2 is vital for priming anti-tumor CD4+ T cells in multiple tumor models. pDC is a unique subset of DCs and produces type I IFN through TLR7 and TLR9. Studies have shown that pDCs are related to immunosuppression in the TME through the secretion of immunosuppressive cytokines and by promoting regulatory T cells. MoDCs differentiate separately from monocytes in response to inflammatory cues and infection. Also, MoDCs can cross-prime CD8+ T cells. In this review, we summarize the subsets and functions of DCs. We also discuss the role of different DC subsets in shaping T cell immunity in TME and targeting DCs for potential immunotherapeutic benefits against cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Cell-based oncotherapies are gaining considerable terrain in the last years thanks to the development of safe and promising treatments against cancer. A better understanding of the roles and functional capacities of cellular immune components displaying antitumor activity will likely potentiate these encouraging results. In this review, we summarize the properties and uses of a particular type of immune cells that recognize lipid-derived determinants presented on the cell surface. Such immune cells, known as invariant Natural Killer T (iNKT) cells have the potential to significantly favor anti-tumoral adaptive immune responses. Currently, they are being extensively evaluated in preclinical settings and may soon reach clinical trials to ameliorate anti-cancer treatments. Invariant natural killer T cells (iNKTs), a type of unconventional T cells, share features with NK cells and have an invariant T cell receptor (TCR), which recognizes lipid antigens loaded on CD1d molecules, a major histocompatibility complex class I (MHC-I)-like protein. This interaction produces the secretion of a wide array of cytokines by these cells, including interferon gamma (IFN-γ) and interleukin 4 (IL-4), allowing iNKTs to link innate with adaptive responses. Interestingly, molecules that bind CD1d have been identified that enable the modulation of these cells, highlighting their potential pro-inflammatory and immunosuppressive capacities, as required in different clinical settings. In this review, we summarize key features of iNKTs and current understandings of modulatory α-galactosylceramide (α-GalCer) variants, a model iNKT cell activator that can shift the outcome of adaptive immune responses. Furthermore, we discuss advances in the development of strategies that modulate these cells to target pathologies that are considerable healthcare burdens. Finally, we recapitulate findings supporting a role for iNKTs in infectious diseases and tumor immunotherapy. [ABSTRACT FROM AUTHOR]