Infiltration of CD163-, PD-L1- and FoxP3-positive cells adversely affects outcome in patients with mantle cell lymphoma independent of established risk factors.

Autor: Rodrigues JM; Department of Immunotechnology, Lund University, Lund, Sweden., Nikkarinen A; Department of Immunology, Genetics and Pathology, Clinical and Experimental Oncology, Uppsala University, Uppsala, Sweden., Hollander P; Department of Immunology, Genetics and Pathology, Clinical and Experimental Oncology, Uppsala University, Uppsala, Sweden., Weibull CE; Department of Medicine, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden., Räty R; Department of Hematology, Helsinki University Hospital, Helsinki, Finland., Kolstad A; Department of Oncology, Oslo University Hospital, Oslo, Norway., Amini RM; Department of Immunology, Genetics and Pathology, Clinical and Experimental Oncology, Uppsala University, Uppsala, Sweden., Porwit A; Department of Clinical Sciences, Oncology and Pathology, Lund University, Lund, Sweden., Jerkeman M; Department of Oncology, Lund University Hospital, Lund, Sweden., Ek S; Department of Immunotechnology, Lund University, Lund, Sweden., Glimelius I; Department of Immunology, Genetics and Pathology, Clinical and Experimental Oncology, Uppsala University, Uppsala, Sweden.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2021 May; Vol. 193 (3), pp. 520-531. Date of Electronic Publication: 2021 Mar 08.
DOI: 10.1111/bjh.17366
Abstrakt: We characterised patients with mantle cell lymphoma (MCL) with poor prognosis based on differences in immune infiltration. Different expressions of the tumour cell markers Cyclin D1 and sex-determining region Y-box transcription factor 11 (SOX11), and the immune markers cluster of differentiation 3 (CD3), CD4, CD8, CD25, forkhead box protein P3 (FoxP3), T-box transcription factor TBX21 (T-bet), programmed cell death protein 1 (PD-1), programmed-death ligand 1 (PD-L1) and CD163 were investigated for all-cause mortality in 282 patients with MCL and time-to-progression (TTP) in 106 clinical trial patients. With increasing age, a significantly lower infiltration of CD3 + T lymphocytes was seen. T-cell infiltration was independent of cellular tumour antigen p53 (p53) expression, Ki-67, morphology and frequency of tumour cells. The all-cause mortality was higher in patients with PD-L1-expression above cut-off [hazard ratio (HR) 1·97, 95% confidence interval (CI) 1·18-3·25, adjusted for sex and MCL International Prognostic Index (MIPI)] and a higher frequency of CD163 + cells (continuously, HR 1·51, 95% CI 1·03-2·23, adjusting for age, sex, morphology, Ki-67 and p53). In patients treated within the Nordic Lymphoma Group MCL2/3 trials, TTP was shorter in patients with a higher frequency of FoxP3 + cells (HR 3·22, 95% CI 1·40-7·43) and CD163 + cells (HR 6·09, 95% CI 1·84-20·21), independent of sex and MIPI. When combined a higher frequency of CD163 + macrophages and PD-L1 + cells or high CD163 + macrophages and FoxP3 + regulatory T cells indicated worse outcome independent of established risk factors. The T-cell infiltrate was in turn independent of molecular characteristics of the malignant cells and decreased with age.
(© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: