Although classical DC (cDC), which are derived from myeloid progenitors,are specialized in antigen processing and (cross)presentation. However, theyalone are sometimes not enough to prime efficient... Show moreAlthough classical DC (cDC), which are derived from myeloid progenitors,are specialized in antigen processing and (cross)presentation. However, theyalone are sometimes not enough to prime efficient CD8+ T-cell responses. Theconcept of DC licensing by CD4+ T-cell “help” for anti-tumor CTL responses wasdiscovered in 1990s. Since then, ample mouse studies have been conducted aimingto discover the mechanism of the “help” signals. In this thesis, I delved intothe molecular mechanisms of CD4+ T-cell “help” as a critical signal that cansuccessfully activate human cDC1 and describe the clinical significance of cDC1licensing in human cancers. I also explored the role of type I interferon(IFN-I) signaling as part of cDC1 licensing machinery, and identified tumor-infiltratingKi67+CXCL13+CD4+ T-cells as IFN-I producers in the context of help delivery tocDC1 in the tumor. With the intention to employ the knowledge of DC biology incancer treatments, I also explored the potential of DC targeting immunotherapies.Lastly, as an integral component of my exploration into DC biology, Iinvestigated how myeloid progenitors respond to both external and internalstress. Show less
