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. 2020 Aug 22;33(1):27–37. doi: 10.1093/intimm/dxaa057

Fig. 3.

Fig. 3.

CD4 T cells relay help-signals via DCs that support CD8 T-cell differentiation in the tumor. (A) Within lymphoid-like niches in the tumor, helper Tfh-like CD4 T cells (blue) which also reside within APC-rich zones in the tumor, can license cDC1 (black) or cDC2 (purple) via CD40–CD40L interactions and secrete soluble factors, such as IL-21 that can help drive terminal differentiation (TD) of stem-like CD8 T cells. (B) Treg cells can secrete immunoregulatory cytokines, such as TGF-β to maintain the stem-like CD8 T-cell population in a quiescent state until the differentiation signal is delivered. Tregs can also block the co-stimulatory signals delivered to the stem-like CD8 T cells via CTLA4 interacting with CD80/86 on cDCs within the tumor. The combination of these signals may act to sustain a stem-like CD8 T-cell population that can be maintained for long periods of time within the tumor while driving the production of terminally differentiated CD8 T cells that maintain cytolytic capacity to control disease progression.