Faculty, Student Works School of Medicinehttp://hdl.handle.net/10713/59802024-03-28T12:22:17Z2024-03-28T12:22:17ZPD-L1 regulation by Dual Oxygenase 2 (DUOX2), a Reactive Oxygen Species (ROS) producing enzyme in gastric cancers.Martins, Mariana B.Carrier, Francehttp://hdl.handle.net/10713/215822024-03-28T05:25:32Z2024-04-05T00:00:00ZPD-L1 regulation by Dual Oxygenase 2 (DUOX2), a Reactive Oxygen Species (ROS) producing enzyme in gastric cancers.
Martins, Mariana B.; Carrier, France
Immune checkpoint inhibitors have shown outstanding activities
in some cancers, but their efficacy is rather variable with limited
long-term response in most patients while others do not respond
well or even develop resistances. The oxidative state of the tumor
and its microenvironment plays a critical role in this response
and highlights the importance of better understanding the role of
redox enzymes in response to immunotherapy. In fact, Reactive
Oxygen Species (ROS) effectors can either up or down regulate
PD-L1 expression depending on their targets and mechanisms of
action. Our data indicate that DUOX2, an NADPH enzyme involved
in the production of H2O2, is expressed in about forty percent of
human gastric cancers and is significantly increased in
esophageal cancers. Moreover, DUOX2 expression in human
gastric and esophageal cancer cells corresponds to down
regulation of the immune checkpoint PD-L1. Conversely, down
regulation of DUOX2 increases PD-L1, HIF-1a and c-Myc
expression in these cells. To better understand the role of
DUOX2 in the production of ROS and how it interferes with the
expressions of HIF-1a and PD-L1, we also evaluated its effects on
the ROS scavenger glutathione (GSH) and the ROS generating
Ceramide in cells expressing or not DUOX2. The down regulation
of DUOX2 reduced by more than half Ceramide levels and
significantly increased GSH levels. This is consistent with the
known effect of H2O2 on Ceramide generation through
sphingomyelin hydrolysis and H2O2 inhibitory effect on HIF-1a
binding and accumulation of HIF-1a protein. Because HIF-1a is a
known regulator of PD-L1, DUOX2 expression on some tumors
could thus interfere with PD-L1 expression through generation of
H2O2. Moreover, because HIF-1a and PD-L1 expression contribute
to radio-resistance, DUOX2 expression could sensitize cancer
cells to radiation therapy. On the other hand, tumors lacking
DUOX2 expression would be expected to be more sensitive to
immunotherapy targeting PD-1 and/or PD-L1. DUOX2 expression
thus appears to hold significant potential as a valuable biomarker
to guide therapeutic decisions regarding radiation or immuno-
therapy
AACR Annual Meeting, April 5-10, 2024
2024-04-05T00:00:00ZOxidative Stress Relates to Negative Symptoms in a Gluten Sensitive Schizophrenia SubgroupKelly, Deanna L.Kim, EunkyoungRedwood, SidneyEaton, William W.Vyas, GopalAdams, Heather A.Harrington, ValeriaRoche, DanielCihakova, DanielaTalor, Monica V.Dadkhoo, DonnaChen, ShouGlassman, MatthewKulaga, Stephanie S.Rodriquez, KatrinaDemyanovich, HaleyHutchinson, OliviaPatterson, BrucePayne, Gregory F.http://hdl.handle.net/10713/215642024-03-21T05:42:25Z2024-04-03T00:00:00ZOxidative Stress Relates to Negative Symptoms in a Gluten Sensitive Schizophrenia Subgroup
Kelly, Deanna L.; Kim, Eunkyoung; Redwood, Sidney; Eaton, William W.; Vyas, Gopal; Adams, Heather A.; Harrington, Valeria; Roche, Daniel; Cihakova, Daniela; Talor, Monica V.; Dadkhoo, Donna; Chen, Shou; Glassman, Matthew; Kulaga, Stephanie S.; Rodriquez, Katrina; Demyanovich, Haley; Hutchinson, Olivia; Patterson, Bruce; Payne, Gregory F.
SIRS Congress, April 3, 2024
2024-04-03T00:00:00ZUtilization of Pseudomonas Eradication Protocols Amongst Lung Transplant CentersSaharia, KapilBaddley, JohnHeil, EmilyPrakash, KatyaCharles, D.Reed, R.Eberlein, M.http://hdl.handle.net/10713/215632024-03-21T05:41:37Z2024-04-11T00:00:00ZUtilization of Pseudomonas Eradication Protocols Amongst Lung Transplant Centers
Saharia, Kapil; Baddley, John; Heil, Emily; Prakash, Katya; Charles, D.; Reed, R.; Eberlein, M.
nternational Society for Heart & Lung Transplantation, April 11, 2024
2024-04-11T00:00:00ZChronic Alcohol Dampens Bidirectional Claustrocortical SignalingWulff, AndreasSheats, Samuel H.Douglass, Eliza A.Mathur, Brian N. (Brian Neil)http://hdl.handle.net/10713/214962024-03-07T02:26:01Z2024-02-10T00:00:00ZChronic Alcohol Dampens Bidirectional Claustrocortical Signaling
Wulff, Andreas; Sheats, Samuel H.; Douglass, Eliza A.; Mathur, Brian N. (Brian Neil)
Gordon Research Conference, February 10, 2024
2024-02-10T00:00:00Z