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

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Rodrigues , J M , Nikkarinen , A , Hollander , P , Weibull , C E , Räty , R , Kolstad , A , Amini , R-M , Porwit , A , Jerkeman , M , Ek , S & Glimelius , I 2021 , ' Infiltration of CD163-, PD-L1-and FoxP3-positive cells adversely affects outcome in patients with mantle cell lymphoma independent of established risk factors ' , British Journal of Haematology , vol. 193 , no. 3 , pp. 520-531 . https://doi.org/10.1111/bjh.17366

Title: Infiltration of CD163-, PD-L1-and FoxP3-positive cells adversely affects outcome in patients with mantle cell lymphoma independent of established risk factors
Author: Rodrigues, Joana M.; Nikkarinen, Anna; Hollander, Peter; Weibull, Caroline E.; Räty, Riikka; Kolstad, Arne; Amini, Rose-Marie; Porwit, Anna; Jerkeman, Mats; Ek, Sara; Glimelius, Ingrid
Contributor organization: HUS Comprehensive Cancer Center
Hematologian yksikkö
Department of Oncology
Date: 2021-05
Language: eng
Number of pages: 12
Belongs to series: British Journal of Haematology
ISSN: 0007-1048
DOI: https://doi.org/10.1111/bjh.17366
URI: http://hdl.handle.net/10138/340323
Abstract: 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 center dot 97, 95% confidence interval (CI) 1 center dot 18-3 center dot 25, adjusted for sex and MCL International Prognostic Index (MIPI)] and a higher frequency of CD163(+) cells (continuously, HR 1 center dot 51, 95% CI 1 center dot 03-2 center dot 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 center dot 22, 95% CI 1 center dot 40-7 center dot 43) and CD163(+) cells (HR 6 center dot 09, 95% CI 1 center dot 84-20 center dot 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.
Subject: CD163
FoxP3
mantle cell lymphoma
microenvironment
PD&#8208
1
L1
3122 Cancers
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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