TY - JOUR
T1 - Racial Differences in the Tumor Immune Landscape and Survival of Women with High-Grade Serous Ovarian Carcinoma
AU - Peres, Lauren C.
AU - Colin-Leitzinger, Christelle
AU - Sinha, Sweta
AU - Marks, Jeffrey R.
AU - Conejo-Garcia, Jose R.
AU - Alberg, Anthony J.
AU - Bandera, Elisa V.
AU - Berchuck, Andrew
AU - Bondy, Melissa L.
AU - Christensen, Brock C.
AU - Cote, Michele L.
AU - Doherty, Jennifer Anne
AU - Moorman, Patricia G.
AU - Peters, Edward S.
AU - Segura, Carlos Moran
AU - Nguyen, Jonathan V.
AU - Schwartz, Ann G.
AU - Terry, Paul D.
AU - Wilson, Christopher M.
AU - Fridley, Brooke L.
AU - Schildkraut, Joellen M.
N1 - Funding Information:
L.C. Peres reports grants from NIH during the conduct of the study. J.R. Conejo-Garcia reports personal fees from Alloy Therapeutics and grants and personal fees from Anixa Biosciences outside the submitted work; in addition, J.R. Conejo-Garcia has a patent for Anixa Biosciences issued to The Wistar Institute and a patent for Compass Therapeutics pending to The Wistar Institute/Compass. A.J. Alberg reports grants from NIH during the conduct of the study. E.V. Bandera reports grants from NIH/NCI during the conduct of the study and is currently serving on Pfizer Clinical Trial Diversity Initiative Advisory Board. B. C. Christensen reports personal fees from University of California San Francisco outside the submitted work. P.G. Moorman reports grants from NCI during the conduct of the study. A.G. Schwartz reports grants from NIH/NCI during the conduct of the study. J.M. Schildkraut reports grants from NIH/NCI during the conduct of the study. No disclosures were reported by the other authors.
Funding Information:
We would like to acknowledge the support of the Advanced Analytical and Digital Pathology Lab in the Pathology Department and the Biostatistics and Bioinformatics Shared Resource at the H. Lee Moffitt Cancer Center and Research Institute, an NCI-designated Comprehensive Cancer Center. We would also like to thank Drs. Jill Barnholtz-Sloan and Ellen Funkhouser for their contributions to the AACES. We acknowledge the AACES interviewers, Christine Bard, LaTonda Briggs, Whitney Franz (North Carolina), and Robin Gold (Detroit). We also acknowledge the individuals responsible for facilitating case ascertainment across the study sites, including Christie McCullum-Hill (Alabama); Rana Bayakly, Vicki Bennett, Judy Andrews, and Debbie Chambers (Georgia); the Louisiana Tumor Registry; Lisa Paddock and Manisha Narang (New Jersey); Diana Slone, Yingli Wolinsky, Steven Waggoner, Anne Heugel, Nancy Fusco, Kelly Ferguson, Peter Rose, Deb Strater, Taryn Ferber, Donna White, Lynn Borzi, Eric Jenison, Nairmeen Haller, Debbie Thomas, Vivian von Gruenigen, Michele McCarroll, Joyce Neading, John Geisler, Stephanie Smiddy, David Cohn, Michele Vaughan, Luis Vaccarello, Elayna Freese, James Pavelka, Pam Plummer, William Nahhas, Ellen Cato, John Moroney, Mark Wysong, Tonia Combs, Marci Bowling, Brandon Fletcher (Ohio); Susan Bolick, Donna Acosta, Catherine Flanagan (South Carolina); Martin Whiteside (Tennessee); and Georgina Armstrong and the Texas Registry, Cancer Epidemiology and Surveillance Branch, Department of State Health Services. This study was supported by K99/R00CA218681 (PI: L.C. Peres). The AACES is supported by R01CA237318 (PI: J.M. Schildkraut, Andrew Lawson) and R01CA142081 (PI: J.M. Schildkraut), and NCOCS is supported by R01CA076016 (PI: J.M. Schildkraut).
Publisher Copyright:
© 2022 American Association for Cancer Research
PY - 2022/5
Y1 - 2022/5
N2 - Background: Tumor-infiltrating lymphocytes (TIL) confer a survival benefit among patients with ovarian cancer; however, little work has been conducted in racially diverse cohorts. Methods: The current study investigated racial differences in the tumor immune landscape and survival of age- and stage-matched non-Hispanic Black and non-Hispanic White women with high-grade serous ovarian carcinoma (HGSOC) enrolled in two population-based studies (n ¼ 121 in each racial group). We measured TILs (CD3þ), cytotoxic T cells (CD3þCD8þ), regulatory T cells (CD3þFoxP3þ), myeloid cells (CD11bþ), and neutrophils (CD11bþCD15þ) via multiplex immunofluorescence. Multivariable Cox proportional hazard regression was used to estimate the association between immune cell abundance and survival overall and by race. Results: Overall, higher levels of TILs, cytotoxic T cells, myeloid cells, and neutrophils were associated with better survival in the intratumoral and peritumoral region, irrespective of tissue compartment (tumor, stroma). Improved survival was noted for T-regulatory cells in the peritumoral region and in the stroma of the intratumoral region, but no association for intratumoral T-regulatory cells. Despite similar abundance of immune cells across racial groups, associations with survival among non-Hispanic White women were consistent with the overall findings, but among non-Hispanic Black women, most associations were attenuated and not statistically significant. Conclusions: Our results add to the existing evidence that a robust immune infiltrate confers a survival advantage among women with HGSOC; however, non-Hispanic Black women may not experience the same survival benefit as non-Hispanic White women with HGSOC. Impact: This study contributes to our understanding of the immunoepidemiology of HGSOC in diverse populations.
AB - Background: Tumor-infiltrating lymphocytes (TIL) confer a survival benefit among patients with ovarian cancer; however, little work has been conducted in racially diverse cohorts. Methods: The current study investigated racial differences in the tumor immune landscape and survival of age- and stage-matched non-Hispanic Black and non-Hispanic White women with high-grade serous ovarian carcinoma (HGSOC) enrolled in two population-based studies (n ¼ 121 in each racial group). We measured TILs (CD3þ), cytotoxic T cells (CD3þCD8þ), regulatory T cells (CD3þFoxP3þ), myeloid cells (CD11bþ), and neutrophils (CD11bþCD15þ) via multiplex immunofluorescence. Multivariable Cox proportional hazard regression was used to estimate the association between immune cell abundance and survival overall and by race. Results: Overall, higher levels of TILs, cytotoxic T cells, myeloid cells, and neutrophils were associated with better survival in the intratumoral and peritumoral region, irrespective of tissue compartment (tumor, stroma). Improved survival was noted for T-regulatory cells in the peritumoral region and in the stroma of the intratumoral region, but no association for intratumoral T-regulatory cells. Despite similar abundance of immune cells across racial groups, associations with survival among non-Hispanic White women were consistent with the overall findings, but among non-Hispanic Black women, most associations were attenuated and not statistically significant. Conclusions: Our results add to the existing evidence that a robust immune infiltrate confers a survival advantage among women with HGSOC; however, non-Hispanic Black women may not experience the same survival benefit as non-Hispanic White women with HGSOC. Impact: This study contributes to our understanding of the immunoepidemiology of HGSOC in diverse populations.
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U2 - 10.1158/1055-9965.EPI-21-1334
DO - 10.1158/1055-9965.EPI-21-1334
M3 - Article
C2 - 35244678
AN - SCOPUS:85129996890
VL - 31
SP - 1006
EP - 1016
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 5
ER -