CD8+ T cells are essential for adaptive immunity against infection and tumors. Their ability to proliferate after stimulation is crucial to their functionality. Dendritic cells (DCs) are professional antigen-presenting cells that induce their proliferation. Here, we show that thapsigargin-induced LAD2 mast cell (MC) line-released products can impair the ability of monocyte-derived DCs to induce CD8+ T-cell proliferation and the generation of Th1 cytokine-producing T cells. We found that culture medium conditioned with LAD2 MCs previously stimulated with thapsigargin (thapsLAD2) induces maturation of DCs as determined by the maturation markers CD80, CD83, CD86, and HLA-DR. However, thapsLAD2-matured DCs produced no detectable TNFα or IL-12 during the maturation. In addition, although their surface expression of PD-L1 was comparable with the immature or TLR7/8-agonist (R848)-matured DCs, their TIM-3 expression was significantly higher than in immature DCs and even much higher than in R848-matured DCs. In addition, contrary to R848-matured DCs, the thapsLAD2-matured DCs only tended to induce enhanced proliferation of CD4+ T cells than immature DCs. For CD8+ T cells, this tendency was not even detected because thapsLAD2-matured and immature DCs comparably induced their proliferation, which contrasted with the significantly enhanced proliferation induced by R848-matured DCs. Furthermore, these differences were comparably recapitulated in the ability of the tested DCs to induce IFNγ- and IFNγ/TNFα-producing T cells. These findings show a novel mechanism of MC-mediated regulation of adaptive immune responses.

• MeSH
• aktivace lymfocytů * účinky léků   imunologie   MeSH
• buněčná diferenciace * účinky léků   MeSH
• buněčné linie MeSH
• buněčný receptor 2 viru hepatitidy A metabolismus   MeSH
• CD8-pozitivní T-lymfocyty * imunologie   účinky léků   MeSH
• cytokiny metabolismus   MeSH
• dendritické buňky * imunologie   účinky léků   metabolismus   MeSH
• imidazoly farmakologie   MeSH
• lidé MeSH
• mastocyty * imunologie   účinky léků   metabolismus   MeSH
• monocyty imunologie   účinky léků   metabolismus   MeSH
• proliferace buněk * účinky léků   MeSH
• thapsigargin * farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• buněčný receptor 2 viru hepatitidy A MeSH
• cytokiny MeSH
• HAVCR2 protein, human MeSH Prohlížeč
• imidazoly MeSH
• thapsigargin * MeSH

The immune checkpoint inhibitors have revolutionized cancer immunotherapy. These inhibitors are game changers in many cancers and for many patients, sometimes show unprecedented therapeutic efficacy. However, their therapeutic efficacy is largely limited in many solid tumors where the tumor-controlled immune microenvironment prevents the immune system from efficiently reaching, recognizing, and eliminating cancer cells. The tumor immune microenvironment is largely orchestrated by immune cells through which tumors gain resistance against the immune system. Among these cells are mast cells and dendritic cells. Both cell types possess enormous capabilities to shape the immune microenvironment. These capabilities stage these cells as cellular checkpoints in the immune microenvironment. Regaining control over these cells in the tumor microenvironment can open new avenues for breaking the resistance of solid tumors to immunotherapy. In this review, we will discuss mast cells and dendritic cells in the context of solid tumors and how these immune cells can, alone or in cooperation, modulate the solid tumor resistance to the immune system. We will also discuss how this modulation could be used in novel immunotherapeutic modalities to weaken the solid tumor resistance to the immune system. This weakening could then help other immunotherapeutic modalities engage against these tumors more efficiently.

• Klíčová slova
• cellular checkpoint, dendritic cells, immunotherapy, mast cells,
• MeSH
• dendritické buňky patologie   MeSH
• imunoterapie MeSH
• inhibitory kontrolních bodů MeSH
• lidé MeSH
• mastocyty * patologie   MeSH
• nádorové mikroprostředí MeSH
• nádory * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• inhibitory kontrolních bodů MeSH