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

James,Nicole E.; James,Nicole E.; Valenzuela,Ashley D.; Valenzuela,Ashley D.; Emerson,Jenna B.; Emerson,Jenna B.; Woodman,Morgan; Woodman,Morgan; Miller,Katherine; Miller,Katherine; Hovanesian,Virginia; Hovanesian,Virginia; Ou,Joyce; Ou,Joyce; Ribeiro,Jennifer R.; Ribeiro,Jennifer R.

doi:10.3892/ol.2022.13308

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

Authors:
- Nicole E. James
- Ashley D. Valenzuela
- Jenna B. Emerson
- Morgan Woodman
- Katherine Miller
- Virginia Hovanesian
- Joyce Ou
- Jennifer R. Ribeiro
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Affiliations: Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, Providence, RI 02903, USA, Rhode Island Hospital, Core Research Laboratories, Women and Infants Hospital, Providence, RI 02903, USA, Warren Alpert Medical School, Brown University, Providence, RI 02903, USA
Published online on: April 26, 2022 https://doi.org/10.3892/ol.2022.13308
Article Number: 188
Copyright: © James et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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‑responsive 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.

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