[PDF][PDF] Telomere stress potentiates STING-dependent anti-tumor immunity
Cancer cell, 2020•cell.com
Telomerase is an attractive target for anti-tumor therapy as it is almost universally expressed
in cancer cells. Here, we show that treatment with a telomere-targeting drug, 6-thio-2′-
deoxyguanosine (6-thio-dG), leads to tumor regression through innate and adaptive immune-
dependent responses in syngeneic and humanized mouse models of telomerase-
expressing cancers. 6-thio-dG treatment causes telomere-associated DNA damages that are
sensed by dendritic cells (DCs) and activates the host cytosolic DNA sensing …
in cancer cells. Here, we show that treatment with a telomere-targeting drug, 6-thio-2′-
deoxyguanosine (6-thio-dG), leads to tumor regression through innate and adaptive immune-
dependent responses in syngeneic and humanized mouse models of telomerase-
expressing cancers. 6-thio-dG treatment causes telomere-associated DNA damages that are
sensed by dendritic cells (DCs) and activates the host cytosolic DNA sensing …
Summary
Telomerase is an attractive target for anti-tumor therapy as it is almost universally expressed in cancer cells. Here, we show that treatment with a telomere-targeting drug, 6-thio-2′-deoxyguanosine (6-thio-dG), leads to tumor regression through innate and adaptive immune-dependent responses in syngeneic and humanized mouse models of telomerase-expressing cancers. 6-thio-dG treatment causes telomere-associated DNA damages that are sensed by dendritic cells (DCs) and activates the host cytosolic DNA sensing STING/interferon I pathway, resulting in enhanced cross-priming capacity of DCs and tumor-specific CD8+ T cell activation. Moreover, 6-thio-dG overcomes resistance to checkpoint blockade in advanced cancer models. Our results unveil how telomere stress increases innate sensing and adaptive anti-tumor immunity and provide strong rationales for combining telomere-targeting therapy with immunotherapy.
cell.com