TY - JOUR
T1 - Intratumoral expression analysis reveals that OX40 and TIM‑3 are prominently expressed and have variable associations with clinical outcomes in high grade serous ovarian cancer
AU - James, Nicole E.
AU - Valenzuela, Ashley D.
AU - Emerson, Jenna B.
AU - Woodman, Morgan
AU - Miller, Katherine
AU - Hovanesian, Virginia
AU - Ou, Joyce
AU - Ribeiro, Jennifer R.
N1 - Funding Information:
The present study was supported by the Rhode Island Hospital Center for Cancer Research Development COBRE Pilot Award supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (grant no. 5P30GM110759); the Division of Gynecologic Oncology, Program in Women's Oncology at Women & Infants Hospital; Swim Across America; the Kilguss Research Core of Women & Infants Hospital, and the COBRE Center for Computational Biology of Human Disease (CBHD) at Brown University. The Kilguss Research Core is supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (grant no. P30GM114750). The COBRE Center for CBHD is supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (grant no. P20GM109035).
Funding Information:
The authors would like to thank Dr Joselynn Wallace (COBRE Center for CBHD, Brown University) for assistance with acquiring TCGA data. The authors would also like to thank Dr Christina Raker (Division of Research, Women and Infants Hospital) for counseling on all statistical analyses performed. The present study was supported by the Rhode Island Hospital Center for Cancer Research Development COBRE Pilot Award supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (grant no. 5P30GM110759); the Division of Gynecologic Oncology, Program in Women's Oncology at Women & Infants Hospital; Swim Across America; the Kilguss Research Core of Women & Infants Hospital, and the COBRE Center for Computational Biology of Human Disease (CBHD) at Brown University. The Kilguss Research Core is supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (grant no. P30GM114750). The COBRE Center for CBHD is supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (grant no. P20GM109035).
Publisher Copyright:
© 2022 Spandidos Publications. All rights reserved.
PY - 2022/6
Y1 - 2022/6
N2 - Patients with ovarian cancer exhibit low response rates to anti‑programmed cell death protein‑1 (PD‑1) based therapies, despite ovarian tumors demonstrating measurable immune responses. Therefore, the aim of the present study was to comparatively examine expression of notable immune co‑stimulatory and co‑inhibitory receptors in order identify the most abundant receptors that could potentially serve as therapeutic targets to enhance immunotherapy response in high grade serous ovarian cancer (HGSOC). The Cancer Genome Atlas (TCGA) was employed to compare levels of various HGSOC and pan‑cancer cohorts. To confirm these findings at the protein level, immunofluorescence of select receptors was performed in 29 HGSOC patient tissue samples. TCGA and Kaplan Meier analysis was employed to determine the association of highly expressed immune receptors with clinical outcomes. TIM‑3 and OX40 exhibited the highest expression in HGSOC at both the gene and protein level, with TIM‑3 demonstrating highest levels on both CD8+ and CD4+ T cell subsets. Pan‑cancer analysis determined that TIM‑3 and OX40 levels were similar to those in immunotherapy‑respon‑ sive cancers, while PD‑1 exhibited much lower expression in HGSOC. Finally, OX40 was most strongly associated with improved patient survival. Overall, the current study suggested that TIM‑3 and OX40 are frequently expressed intratumoral immune receptors in HGSOC and thus represent promising immune targets. Furthermore, the present analysis strongly suggested that OX40 was significantly associated with a longer survival and could potentially be utilized as a prognostic factor for improved patient outcomes in HGSOC.
AB - Patients with ovarian cancer exhibit low response rates to anti‑programmed cell death protein‑1 (PD‑1) based therapies, despite ovarian tumors demonstrating measurable immune responses. Therefore, the aim of the present study was to comparatively examine expression of notable immune co‑stimulatory and co‑inhibitory receptors in order identify the most abundant receptors that could potentially serve as therapeutic targets to enhance immunotherapy response in high grade serous ovarian cancer (HGSOC). The Cancer Genome Atlas (TCGA) was employed to compare levels of various HGSOC and pan‑cancer cohorts. To confirm these findings at the protein level, immunofluorescence of select receptors was performed in 29 HGSOC patient tissue samples. TCGA and Kaplan Meier analysis was employed to determine the association of highly expressed immune receptors with clinical outcomes. TIM‑3 and OX40 exhibited the highest expression in HGSOC at both the gene and protein level, with TIM‑3 demonstrating highest levels on both CD8+ and CD4+ T cell subsets. Pan‑cancer analysis determined that TIM‑3 and OX40 levels were similar to those in immunotherapy‑respon‑ sive cancers, while PD‑1 exhibited much lower expression in HGSOC. Finally, OX40 was most strongly associated with improved patient survival. Overall, the current study suggested that TIM‑3 and OX40 are frequently expressed intratumoral immune receptors in HGSOC and thus represent promising immune targets. Furthermore, the present analysis strongly suggested that OX40 was significantly associated with a longer survival and could potentially be utilized as a prognostic factor for improved patient outcomes in HGSOC.
KW - high grade serous ovarian cancer
KW - OX40
KW - TIM-3
UR - http://www.scopus.com/inward/record.url?scp=85131313654&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85131313654&partnerID=8YFLogxK
U2 - 10.3892/ol.2022.13308
DO - 10.3892/ol.2022.13308
M3 - Article
AN - SCOPUS:85131313654
SN - 1792-1074
VL - 23
JO - Oncology Letters
JF - Oncology Letters
IS - 6
M1 - 188
ER -