Matches in SemOpenAlex for { <https://semopenalex.org/work/W4200215809> ?p ?o ?g. }
- W4200215809 abstract "Despite the promising activity of poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) in many cancer types with defects in the DNA damage response the majority of the treated patients acquire PARPi resistance and succumb to their diseases. Consequently, there is an urgent need to identify the mechanisms of PARPi resistance. Here, we show that PARPi treatment promotes STAT3 activation in ovarian cancer cells, tumor-associated immune cells and fibroblasts, resulting in PARPi resistance and immunosuppression. Comparison of ovarian cancer patient-matched tumor biopsies before and after PARPi therapy revealed that STAT3 activity was significantly higher in tumor cells and tumor-associated immune cells and fibroblasts post PARPi treatment. Moreover, one-time PARPi treatment activated STAT3 both in tumor cells as well as diverse immune subsets and fibroblasts. PARPi-treated immune cells exhibited decreased expression of immunostimulatory interferon (IFN)-γ and Granzyme B while increasing immunosuppressive cytokine IL-10. Finally, we demonstrate that the acquisition of PARPi resistance in ovarian cancer cells was accompanied by increased STAT3 activity. Ablating STAT3 inhibited PARPi-resistant ovarian tumor cell growth and/or restored PARPi sensitivity. Therefore, our study has identified a critical mechanism intrinsic to PARPi that promotes resistance to PARPi and induces immunosuppression during PARPi treatment by activating STAT3 in tumor cells and tumor-associated immune cells/fibroblasts." @default.
- W4200215809 created "2021-12-31" @default.
- W4200215809 creator A5012334511 @default.
- W4200215809 creator A5021119678 @default.
- W4200215809 creator A5026847104 @default.
- W4200215809 creator A5029466011 @default.
- W4200215809 creator A5030899790 @default.
- W4200215809 creator A5046159625 @default.
- W4200215809 creator A5050397008 @default.
- W4200215809 creator A5051087307 @default.
- W4200215809 creator A5067750617 @default.
- W4200215809 creator A5082756867 @default.
- W4200215809 date "2021-12-07" @default.
- W4200215809 modified "2023-10-18" @default.
- W4200215809 title "PARP Inhibition Activates STAT3 in Both Tumor and Immune Cells Underlying Therapy Resistance and Immunosuppression In Ovarian Cancer" @default.
- W4200215809 cites W1960585934 @default.
- W4200215809 cites W1973268287 @default.
- W4200215809 cites W1979051608 @default.
- W4200215809 cites W1982334431 @default.
- W4200215809 cites W1983470102 @default.
- W4200215809 cites W1987520066 @default.
- W4200215809 cites W1994464552 @default.
- W4200215809 cites W2007841824 @default.
- W4200215809 cites W2009007206 @default.
- W4200215809 cites W2026324708 @default.
- W4200215809 cites W2027111183 @default.
- W4200215809 cites W2030503662 @default.
- W4200215809 cites W2031268426 @default.
- W4200215809 cites W2039290676 @default.
- W4200215809 cites W2044227662 @default.
- W4200215809 cites W2067117419 @default.
- W4200215809 cites W2073002157 @default.
- W4200215809 cites W2074601175 @default.
- W4200215809 cites W2085138770 @default.
- W4200215809 cites W2088801927 @default.
- W4200215809 cites W2093485788 @default.
- W4200215809 cites W2100525241 @default.
- W4200215809 cites W2102365935 @default.
- W4200215809 cites W2125933228 @default.
- W4200215809 cites W2126150441 @default.
- W4200215809 cites W2128822995 @default.
- W4200215809 cites W2130393835 @default.
- W4200215809 cites W2136722399 @default.
- W4200215809 cites W2143082339 @default.
- W4200215809 cites W2149769603 @default.
- W4200215809 cites W2153086428 @default.
- W4200215809 cites W2166103049 @default.
- W4200215809 cites W2168478794 @default.
- W4200215809 cites W2180527932 @default.
- W4200215809 cites W2329531543 @default.
- W4200215809 cites W2341757884 @default.
- W4200215809 cites W2342880373 @default.
- W4200215809 cites W2400022769 @default.
- W4200215809 cites W2435180223 @default.
- W4200215809 cites W2472306545 @default.
- W4200215809 cites W2593659832 @default.
- W4200215809 cites W2742440809 @default.
- W4200215809 cites W2765195183 @default.
- W4200215809 cites W2783142245 @default.
- W4200215809 cites W2797333226 @default.
- W4200215809 cites W2898088739 @default.
- W4200215809 cites W2899414628 @default.
- W4200215809 cites W2900248192 @default.
- W4200215809 cites W2900951833 @default.
- W4200215809 cites W2914911973 @default.
- W4200215809 cites W2942052760 @default.
- W4200215809 cites W2949336848 @default.
- W4200215809 cites W2950564916 @default.
- W4200215809 cites W2951058429 @default.
- W4200215809 cites W2968820602 @default.
- W4200215809 cites W2970135300 @default.
- W4200215809 cites W2996091824 @default.
- W4200215809 cites W3006223213 @default.
- W4200215809 cites W3044025582 @default.
- W4200215809 cites W3087992083 @default.
- W4200215809 cites W3112241528 @default.
- W4200215809 doi "https://doi.org/10.3389/fonc.2021.724104" @default.
- W4200215809 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34956861" @default.
- W4200215809 hasPublicationYear "2021" @default.
- W4200215809 type Work @default.
- W4200215809 citedByCount "11" @default.
- W4200215809 countsByYear W42002158092022 @default.
- W4200215809 countsByYear W42002158092023 @default.
- W4200215809 crossrefType "journal-article" @default.
- W4200215809 hasAuthorship W4200215809A5012334511 @default.
- W4200215809 hasAuthorship W4200215809A5021119678 @default.
- W4200215809 hasAuthorship W4200215809A5026847104 @default.
- W4200215809 hasAuthorship W4200215809A5029466011 @default.
- W4200215809 hasAuthorship W4200215809A5030899790 @default.
- W4200215809 hasAuthorship W4200215809A5046159625 @default.
- W4200215809 hasAuthorship W4200215809A5050397008 @default.
- W4200215809 hasAuthorship W4200215809A5051087307 @default.
- W4200215809 hasAuthorship W4200215809A5067750617 @default.
- W4200215809 hasAuthorship W4200215809A5082756867 @default.
- W4200215809 hasBestOaLocation W42002158091 @default.
- W4200215809 hasConcept C121608353 @default.
- W4200215809 hasConcept C126322002 @default.
- W4200215809 hasConcept C203014093 @default.
- W4200215809 hasConcept C2777701055 @default.
- W4200215809 hasConcept C2780252810 @default.