Targetable Immune Regulatory Molecule Expression in High-Grade Serous Ovarian Carcinomas in African American Women

A Study of PD-L1 and IDO in 112 Cases from the African American Cancer Epidemiology Study (AACES)

Anne M. Mills, Lauren C. Peres, Alice Meiss, Kari L. Ring, Susan C. Modesitt, Sarah E. Abbott, Anthony J. Alberg, Elisa V. Bandera, Jill Barnholtz-Sloan, Melissa L. Bondy, Michele L. Cote, Ellen Funkhouser, Patricia G. Moorman, Edward S. Peters, Ann G. Schwartz, Paul Terry, Kristin Wallace, Joellen M. Schildkraut

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

African American women with high-grade serous ovarian carcinoma have worse outcomes compared with women of European descent. Although the discrepancy is partially attributed to differences in access to care, the tumor immune microenvironment may also contribute. Expression of targetable immune regulatory molecules such as programmed cell death ligand-1 (PD-L1) and indoleamine 2,3 dioxygenase (IDO) is of particular interest as it may help guide therapy in this population. Using cases from the largest study of African American women with ovarian cancer, the African American Cancer Epidemiology Study, we characterized PD-L1 and IDO expression in 112 high-grade serous ovarian carcinomas. Immunohistochemistry for PD-L1, IDO, CD8, FOX3p, and CD68 was performed. PD-L1 and IDO were scored as the percentage of positive tumor cells and tumor-associated immune cells. CD8 and FOX3p counts were averaged across 10 high-power fields. Cox proportional hazards regression was used to evaluate the association between PD-L1 and IDO expression and survival. Tumor cells were positive for PD-L1 and IDO in 29% and 58% of cases, respectively. The majority showed <10% staining, and no cases exceeded 25% positivity. The majority of PD-L1-positive cases coexpressed IDO. PD-L1 and IDO expression was associated with higher CD8 and FOX3p counts (P<0.05). No association was observed between PD-L1 and IDO and survival. In summary, expression of PD-L1 and IDO is seen in a subset of high-grade serous ovarian carcinoma from African American women and is correlated with elevated lymphocyte infiltration. While PD-L1 and IDO co-expression suggests a role for dual immunotherapy, diffuse expression of PD-L1 and IDO is rare, invoking caution regarding the potential for immunotherapeutic response.

Original languageEnglish (US)
Pages (from-to)157-170
Number of pages14
JournalInternational Journal of Gynecological Pathology
Volume38
Issue number2
DOIs
StatePublished - Mar 1 2019

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Indoleamine-Pyrrole 2,3,-Dioxygenase
African Americans
Epidemiology
Cell Death
Ligands
Carcinoma
Neoplasms
Tumor Microenvironment
Survival
Ovarian Neoplasms
Immunotherapy

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Obstetrics and Gynecology

Cite this

Targetable Immune Regulatory Molecule Expression in High-Grade Serous Ovarian Carcinomas in African American Women : A Study of PD-L1 and IDO in 112 Cases from the African American Cancer Epidemiology Study (AACES). / Mills, Anne M.; Peres, Lauren C.; Meiss, Alice; Ring, Kari L.; Modesitt, Susan C.; Abbott, Sarah E.; Alberg, Anthony J.; Bandera, Elisa V.; Barnholtz-Sloan, Jill; Bondy, Melissa L.; Cote, Michele L.; Funkhouser, Ellen; Moorman, Patricia G.; Peters, Edward S.; Schwartz, Ann G.; Terry, Paul; Wallace, Kristin; Schildkraut, Joellen M.

In: International Journal of Gynecological Pathology, Vol. 38, No. 2, 01.03.2019, p. 157-170.

Research output: Contribution to journalArticle

Mills, AM, Peres, LC, Meiss, A, Ring, KL, Modesitt, SC, Abbott, SE, Alberg, AJ, Bandera, EV, Barnholtz-Sloan, J, Bondy, ML, Cote, ML, Funkhouser, E, Moorman, PG, Peters, ES, Schwartz, AG, Terry, P, Wallace, K & Schildkraut, JM 2019, 'Targetable Immune Regulatory Molecule Expression in High-Grade Serous Ovarian Carcinomas in African American Women: A Study of PD-L1 and IDO in 112 Cases from the African American Cancer Epidemiology Study (AACES)', International Journal of Gynecological Pathology, vol. 38, no. 2, pp. 157-170. https://doi.org/10.1097/PGP.0000000000000494
Mills, Anne M. ; Peres, Lauren C. ; Meiss, Alice ; Ring, Kari L. ; Modesitt, Susan C. ; Abbott, Sarah E. ; Alberg, Anthony J. ; Bandera, Elisa V. ; Barnholtz-Sloan, Jill ; Bondy, Melissa L. ; Cote, Michele L. ; Funkhouser, Ellen ; Moorman, Patricia G. ; Peters, Edward S. ; Schwartz, Ann G. ; Terry, Paul ; Wallace, Kristin ; Schildkraut, Joellen M. / Targetable Immune Regulatory Molecule Expression in High-Grade Serous Ovarian Carcinomas in African American Women : A Study of PD-L1 and IDO in 112 Cases from the African American Cancer Epidemiology Study (AACES). In: International Journal of Gynecological Pathology. 2019 ; Vol. 38, No. 2. pp. 157-170.
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abstract = "African American women with high-grade serous ovarian carcinoma have worse outcomes compared with women of European descent. Although the discrepancy is partially attributed to differences in access to care, the tumor immune microenvironment may also contribute. Expression of targetable immune regulatory molecules such as programmed cell death ligand-1 (PD-L1) and indoleamine 2,3 dioxygenase (IDO) is of particular interest as it may help guide therapy in this population. Using cases from the largest study of African American women with ovarian cancer, the African American Cancer Epidemiology Study, we characterized PD-L1 and IDO expression in 112 high-grade serous ovarian carcinomas. Immunohistochemistry for PD-L1, IDO, CD8, FOX3p, and CD68 was performed. PD-L1 and IDO were scored as the percentage of positive tumor cells and tumor-associated immune cells. CD8 and FOX3p counts were averaged across 10 high-power fields. Cox proportional hazards regression was used to evaluate the association between PD-L1 and IDO expression and survival. Tumor cells were positive for PD-L1 and IDO in 29{\%} and 58{\%} of cases, respectively. The majority showed <10{\%} staining, and no cases exceeded 25{\%} positivity. The majority of PD-L1-positive cases coexpressed IDO. PD-L1 and IDO expression was associated with higher CD8 and FOX3p counts (P<0.05). No association was observed between PD-L1 and IDO and survival. In summary, expression of PD-L1 and IDO is seen in a subset of high-grade serous ovarian carcinoma from African American women and is correlated with elevated lymphocyte infiltration. While PD-L1 and IDO co-expression suggests a role for dual immunotherapy, diffuse expression of PD-L1 and IDO is rare, invoking caution regarding the potential for immunotherapeutic response.",
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