Reversing Immunotherapy Resistance in Ovarian Cancer by Targeting a Novel Immune Suppressive Factor Released by Tumor Associated Macrophages (TAMs)
Technical Report,15 Apr 2018,14 Apr 2019
MaineHealth Portland United States
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Our studies have led to the establishment of a variant of the ID8 ovarian tumor model ID8-VEGF that has allowed us to develop important new insight into why subcutaneously implanted ID8 tumors regress over time. To this end, our new data is consistent with an early infiltration of activated CD8 T-cells that contribute to controlling tumor growth, as depleting CD8 T-cells slowed spontaneous regression and enhanced tumor size. Our data suggest for the first time that ID8 and SKOV-3 tumor cells can generate the low molecular weight RGDKGE collagen fragment themselves. These novel findings suggest the presence of an autocrine signaling mechanism that may regulate YAP activity in these tumor cells. Collectively, these observations provide evidence for a role for a hippo-dependent signaling mechanism by which the XL313 collagen fragment regulates ovarian tumor growth. Taken together, our data provides new mechanistic insight that may help optimize the use of Mab XL313 to treat ovarian cancer.
- Medicine and Medical Research