Joerg Uwe Schmohl1,2, Tina Nuebling2,3, Julia Wild2,3, Tanja Kroell4, Lothar Kanz2, Helmut Rainer Salih2,3, Helga Schmetzer4. 1. Section of Molecular Cancer Therapeutics, Therapeutic Radiology-Radiation Oncology, University of Minnesota, Masonic Cancer Center, Minneapolis, MN, USA. 2. Department for Hematology and Oncology, Med Dept II, University Hospital of Tuebingen, Tuebingen, Germany. 3. Clinical Collaboration Unit Translational Immunology, German Cancer Consortium and German Cancer Research Center, Partner site Tuebingen, Department for Internal Medicine II, Eberhard Karls University Tuebingen, Tuebingen, Germany. 4. Department for Hematopoetic Cell Transplantation, Med. Dept.III, University Hospital of Munich, Munich, Germany.
Abstract
BACKGROUND: Co-stimulatory receptor (COR) and ligand (COL) expression on immune effectors are known to be relevant for immunological interactions and might be of prognostic relevance if expressed on acute myeloid leukemia (AML) blasts as reported for receptors of the tumor necrosis factor receptor family. AIM AND METHODS: Antigen expression profiling of COR (RANK, PD-1), COL (RANK-L, PD-1L), and HLA-ABC-antigens on blasts from 90 AML-patients at first diagnosis was performed by flow cytometry (SFI-Level characterization) and findings were correlated with clinical parameters. RESULTS: RANK expression was higher in immature compared to mature FAB groups (P = 0.08). As a monocytic marker, we identified HLA-ABC (P = 0.07). Prognostic analysis revealed a higher probability of overall survival in cases with lower RANK-L expression (<1.6 and ≥1.6, 15.6 vs. 12.2 months, P = 0.008, hazard ratio 0.36, P = 0.008). No significant impact of PD-1/L expression for patients'(pts) survival was seen but a correlation of PD-1 with a secondary AML (P = 0.03). Prolonged disease-free survival however correlated with higher PD-1 expression (≥1.1 vs. <1.1, 31.4 vs. 12.7 months; P = 0.03). CONCLUSION: Our study revealed that RANK-L is a promising marker to forecast pts' prognosis in AML. Immune checkpoint receptor PD-1/L as well as RANK and HLA-ABC did not show an impact on pts' survival.
BACKGROUND: Co-stimulatory receptor (COR) and ligand (COL) expression on immune effectors are known to be relevant for immunological interactions and might be of prognostic relevance if expressed on acute myeloid leukemia (AML) blasts as reported for receptors of the tumor necrosis factor receptor family. AIM AND METHODS: Antigen expression profiling of COR (RANK, PD-1), COL (RANK-L, PD-1L), and HLA-ABC-antigens on blasts from 90 AML-patients at first diagnosis was performed by flow cytometry (SFI-Level characterization) and findings were correlated with clinical parameters. RESULTS: RANK expression was higher in immature compared to mature FAB groups (P = 0.08). As a monocytic marker, we identified HLA-ABC (P = 0.07). Prognostic analysis revealed a higher probability of overall survival in cases with lower RANK-L expression (<1.6 and ≥1.6, 15.6 vs. 12.2 months, P = 0.008, hazard ratio 0.36, P = 0.008). No significant impact of PD-1/L expression for patients'(pts) survival was seen but a correlation of PD-1 with a secondary AML (P = 0.03). Prolonged disease-free survival however correlated with higher PD-1 expression (≥1.1 vs. <1.1, 31.4 vs. 12.7 months; P = 0.03). CONCLUSION: Our study revealed that RANK-L is a promising marker to forecast pts' prognosis in AML. Immune checkpoint receptor PD-1/L as well as RANK and HLA-ABC did not show an impact on pts' survival.
Authors: Mick J M van Eijs; Lotte E van der Wagen; Rogier Mous; Roos J Leguit; Lisette van de Corput; Anne S R van Lindert; Britt B M Suelmann; Anna M Kamphuis; Stefan Nierkens; Karijn P M Suijkerbuijk Journal: Cancer Immunol Immunother Date: 2022-06-13 Impact factor: 6.630