Fig. 9: Ceralasertib treatment schedule results in diverse effects within the tumor microenvironment. | Nature Communications

Fig. 9: Ceralasertib treatment schedule results in diverse effects within the tumor microenvironment.

From: The ATR inhibitor ceralasertib potentiates cancer checkpoint immunotherapy by regulating the tumor microenvironment

Fig. 9

Ceralasertib treatment reduces tumor cell proliferation and depletes exhausted CD8+ T cells, M-MDSC and TAM by inhibiting ATR function in cells with replication stress. Treatment also induces type I IFN that neutralizes suppressive activity of M-MDSC and PMN-MDSC, activates DCs, up-regulate PD-1 expression on T cells, and enhances the inhibitory effect of ATRi on tumor cell proliferation. Intermittent scheduling of ceralasertib allows for appearance of newly generated functionally competent T cells. These T cells enter tumor microenvironment with activated of DCs, decreased presence of immune suppressive myeloid cells, and less potently proliferating tumor cells. Combination of these factors makes T cells more effective in recognizing tumor antigens. Increased PD-1 expression makes these T cells more susceptible to check-point inhibitors, which result in potent antitumor effect.

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