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CD163+ macrophages in mantle cell lymphoma induce activation of prosurvival pathways and immune suppression

de Matos Rodrigues, Joana LU ; Lokhande, Lavanya LU ; Olsson, Lina M LU ; Hassan, May LU ; Johansson, Angelica LU orcid ; Janská, Anna LU ; Kumar, Darshan ; Schmidt, Lina LU ; Nikkarinen, Anna and Hollander, Peter , et al. (2024) In Blood Advances 8(16). p.4370-4385
Abstract

Mantle cell lymphoma (MCL) is dependent on a supportive tumor immune microenvironment (TIME) in which infiltration of CD163+ macrophages has a negative prognostic impact. This study explores how abundance and spatial localization of CD163+ cells are associated with the biology of MCL, using spatial multiomic investigations of tumor and infiltrating CD163+ and CD3+ cells. A total of 63 proteins were measured using GeoMx digital spatial profiling in tissue microarrays from 100 diagnostic MCL tissues. Regions of interest were selected in tumor-rich and tumor-sparse tissue regions. Molecular profiling of CD163+ macrophages, CD20+ MCL cells, and CD3+ T-cells was performed. To validate protein profiles, 1811 messenger RNAs were measured in... (More)

Mantle cell lymphoma (MCL) is dependent on a supportive tumor immune microenvironment (TIME) in which infiltration of CD163+ macrophages has a negative prognostic impact. This study explores how abundance and spatial localization of CD163+ cells are associated with the biology of MCL, using spatial multiomic investigations of tumor and infiltrating CD163+ and CD3+ cells. A total of 63 proteins were measured using GeoMx digital spatial profiling in tissue microarrays from 100 diagnostic MCL tissues. Regions of interest were selected in tumor-rich and tumor-sparse tissue regions. Molecular profiling of CD163+ macrophages, CD20+ MCL cells, and CD3+ T-cells was performed. To validate protein profiles, 1811 messenger RNAs were measured in CD20+ cells and 2 subsets of T cells. Image analysis was used to extract the phenotype and position of each targeted cell, thereby allowing the exploration of cell frequencies and cellular neighborhoods. Proteomic investigations revealed that CD163+ cells modulate their immune profile depending on their localization and that the immune inhibitory molecules, V-domain immunoglobulin suppressor of T-cell activation and B7 homolog 3, have higher expression in tumor-sparse than in tumor-rich tissue regions and that targeting should be explored. We showed that MCL tissues with more abundant infiltration of CD163+ cells have a higher proteomic and transcriptional expression of key components of the MAPK pathway. Thus, the MAPK pathway may be a feasible therapeutic target in patients with MCL with CD163+ cell infiltration. We further showed the independent and combined prognostic values of CD11c and CD163 beyond established risk factors.

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type
Contribution to journal
publication status
published
subject
keywords
Humans, Lymphoma, Mantle-Cell/immunology, Receptors, Cell Surface/metabolism, Antigens, Differentiation, Myelomonocytic/metabolism, Macrophages/metabolism, Antigens, CD/metabolism, Tumor Microenvironment/immunology, Signal Transduction
in
Blood Advances
volume
8
issue
16
pages
16 pages
publisher
American Society of Hematology
external identifiers
  • scopus:85203011008
  • pmid:38959399
ISSN
2473-9529
DOI
10.1182/bloodadvances.2023012039
language
English
LU publication?
yes
additional info
© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
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4f97a648-6e40-41c2-bdf7-267ea14f6370
date added to LUP
2024-09-13 13:39:05
date last changed
2025-05-11 02:05:56
@article{4f97a648-6e40-41c2-bdf7-267ea14f6370,
  abstract     = {{<p>Mantle cell lymphoma (MCL) is dependent on a supportive tumor immune microenvironment (TIME) in which infiltration of CD163+ macrophages has a negative prognostic impact. This study explores how abundance and spatial localization of CD163+ cells are associated with the biology of MCL, using spatial multiomic investigations of tumor and infiltrating CD163+ and CD3+ cells. A total of 63 proteins were measured using GeoMx digital spatial profiling in tissue microarrays from 100 diagnostic MCL tissues. Regions of interest were selected in tumor-rich and tumor-sparse tissue regions. Molecular profiling of CD163+ macrophages, CD20+ MCL cells, and CD3+ T-cells was performed. To validate protein profiles, 1811 messenger RNAs were measured in CD20+ cells and 2 subsets of T cells. Image analysis was used to extract the phenotype and position of each targeted cell, thereby allowing the exploration of cell frequencies and cellular neighborhoods. Proteomic investigations revealed that CD163+ cells modulate their immune profile depending on their localization and that the immune inhibitory molecules, V-domain immunoglobulin suppressor of T-cell activation and B7 homolog 3, have higher expression in tumor-sparse than in tumor-rich tissue regions and that targeting should be explored. We showed that MCL tissues with more abundant infiltration of CD163+ cells have a higher proteomic and transcriptional expression of key components of the MAPK pathway. Thus, the MAPK pathway may be a feasible therapeutic target in patients with MCL with CD163+ cell infiltration. We further showed the independent and combined prognostic values of CD11c and CD163 beyond established risk factors.</p>}},
  author       = {{de Matos Rodrigues, Joana and Lokhande, Lavanya and Olsson, Lina M and Hassan, May and Johansson, Angelica and Janská, Anna and Kumar, Darshan and Schmidt, Lina and Nikkarinen, Anna and Hollander, Peter and Glimelius, Ingrid and Porwit, Anna and Gerdtsson, Anna Sandstrom and Jerkeman, Mats and Ek, Sara}},
  issn         = {{2473-9529}},
  keywords     = {{Humans; Lymphoma, Mantle-Cell/immunology; Receptors, Cell Surface/metabolism; Antigens, Differentiation, Myelomonocytic/metabolism; Macrophages/metabolism; Antigens, CD/metabolism; Tumor Microenvironment/immunology; Signal Transduction}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{16}},
  pages        = {{4370--4385}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood Advances}},
  title        = {{CD163+ macrophages in mantle cell lymphoma induce activation of prosurvival pathways and immune suppression}},
  url          = {{http://dx.doi.org/10.1182/bloodadvances.2023012039}},
  doi          = {{10.1182/bloodadvances.2023012039}},
  volume       = {{8}},
  year         = {{2024}},
}