High PD-L2 Predicts Early Recurrence of ER-Positive Breast Cancer.

Autor:	Chervoneva I; Division of Biostatistics, Thomas Jefferson University, Philadelphia, PA., Peck AR; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI., Sun Y; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI., Yi M; Division of Biostatistics, Thomas Jefferson University, Philadelphia, PA., Udhane SS; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI., Langenheim JF; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI., Girondo MA; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI., Jorns JM; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI., Chaudhary LN; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI., Kamaraju S; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI., Bergom C; Department Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI., Flister MJ; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI., Hooke JA; John P. Murtha Cancer Center, Uniformed Services University, Bethesda, MD., Kovatich AJ; John P. Murtha Cancer Center, Uniformed Services University, Bethesda, MD., Shriver CD; John P. Murtha Cancer Center, Uniformed Services University, Bethesda, MD., Hu H; Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA., Palazzo JP; Department of Pathology, Thomas Jefferson University, Philadelphia, PA., Bibbo M; Department of Pathology, Thomas Jefferson University, Philadelphia, PA., Hyslop T; Center for Health Equity, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA., Nevalainen MT; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI., Pestell RG; Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, Doylestown, PA.; The Wistar Cancer Center, Philadelphia, PA., Fuchs SY; Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, PA., Mitchell EP; Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA., Rui H; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2023 Jan; Vol. 7, pp. e2100498.
DOI:	10.1200/PO.21.00498
Abstrakt:	Purpose: T-cell-mediated cytotoxicity is suppressed when programmed cell death-1 (PD-1) is bound by PD-1 ligand-1 (PD-L1) or PD-L2. Although PD-1 inhibitors have been approved for triple-negative breast cancer, the lower response rates of 25%-30% in estrogen receptor-positive (ER+) breast cancer will require markers to identify likely responders. The focus of this study was to evaluate whether PD-L2, which has higher affinity than PD-L1 for PD-1, is a predictor of early recurrence in ER+ breast cancer. Methods: PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, localized or locoregional ER+ breast cancers were measured retrospectively by quantitative immunofluorescence histocytometry and correlated with progression-free survival (PFS) in the main study cohort (n = 684) and in an independent validation cohort (n = 273). All patients subsequently received standard-of-care adjuvant therapy without immune checkpoint inhibitors. Results: Univariate analysis of the main cohort revealed that high PD-L2 expression in cancer cells was associated with shorter PFS (hazard ratio [HR], 1.8; 95% CI, 1.3 to 2.6; P = .001), which was validated in an independent cohort (HR, 2.3; 95% CI, 1.1 to 4.8; P = .026) and remained independently predictive after multivariable adjustment for common clinicopathological variables (HR, 2.0; 95% CI, 1.4 to 2.9; P < .001). Subanalysis of the ER+ breast cancer patients treated with adjuvant chemotherapy (n = 197) revealed that high PD-L2 levels in cancer cells associated with short PFS in univariate (HR, 2.5; 95% CI, 1.4 to 4.4; P = .003) and multivariable analyses (HR, 3.4; 95% CI, 1.9 to 6.2; P < .001). Conclusion: Up to one third of treatment-naive ER+ breast tumors expressed high PD-L2 levels, which independently predicted poor clinical outcome, with evidence of further elevated risk of progression in patients who received adjuvant chemotherapy. Collectively, these data warrant studies to gain a deeper understanding of PD-L2 in the progression of ER+ breast cancer and may provide rationale for immune checkpoint blockade for this patient group.
Databáze:	MEDLINE
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