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Immune-cell infiltration in high-grade soft tissue sarcomas; prognostic implications of tumor-associated macrophages and B-cells

Nyström, Helena LU ; Jönsson, Mats LU ; Nilbert, Mef LU and Carneiro, Ana LU orcid (2023) In Acta Oncologica 62(1). p.33-39
Abstract

Background: Soft tissue sarcomas are rare, morphologically, and genetically heterogenous. Though the tumors display abundant tumor stroma with infiltrating immune cells, the prognostic impact of various immunologic markers in sarcoma remains poorly defined. We aimed to characterize the immune landscape of a treatment-naïve cohort of soft tissue sarcoma of the extremities and the trunk wall with correlations to metastasis-free survival. Materials and Methods: We surveyed immunohistochemical expression patterns for CD163, CD20, CD3, CD8, and FOXP3 in 134 adult high-grade leiomyosarcomas, liposarcomas, and synovial sarcomas. Results: Macrophages outnumbered tumor-infiltrating lymphocytes. High CD163 infiltration was identified in 49% of... (More)

Background: Soft tissue sarcomas are rare, morphologically, and genetically heterogenous. Though the tumors display abundant tumor stroma with infiltrating immune cells, the prognostic impact of various immunologic markers in sarcoma remains poorly defined. We aimed to characterize the immune landscape of a treatment-naïve cohort of soft tissue sarcoma of the extremities and the trunk wall with correlations to metastasis-free survival. Materials and Methods: We surveyed immunohistochemical expression patterns for CD163, CD20, CD3, CD8, and FOXP3 in 134 adult high-grade leiomyosarcomas, liposarcomas, and synovial sarcomas. Results: Macrophages outnumbered tumor-infiltrating lymphocytes. High CD163 infiltration was identified in 49% of the tumors and was overrepresented (66%) in leiomyosarcoma compared to liposarcoma (46%) and synovial sarcoma (9%). Tumor-grade also correlated with CD163 positivity with high expression in 53% of the high-grade lesions and 28% in low-grade tumors. Infiltrating CD3, CD8 and FOXP3-positive T-cells were significantly more prevalent in leiomyosarcomas than in liposarcomas/synovial sarcomas. CD20+ B-cells were identified only in 14% of the STS. Correlation to established prognostic factors revealed a correlation between CD163+ macrophages and necrosis and predicted an increased risk of metastases. No correlation between CD20+ B-cells and known prognostic factors could be established, though CD20+ B-cells infiltration predicted improved overall survival. Conclusion: We confirm that tumor-infiltrating macrophages outnumber tumor-infiltrating lymphocytes in soft tissue sarcoma and signify an increased risk of metastasis. CD20+ B-cells are scarce in STS and correlate to improved survival. To date, immunotherapeutic strategies directed against T-cells have shown limited effect in soft tissue sarcoma. Our observations suggest that immunomodulatory agents focusing on macrophages may be worthwhile for further investigations in this tumor type. Further studies exploring the prognostic and predictive significance of CD20+ B cells are warranted.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cd163, cd20, sts, tam, tme
in
Acta Oncologica
volume
62
issue
1
pages
7 pages
publisher
Taylor & Francis
external identifiers
  • scopus:85148306743
  • pmid:36786033
ISSN
0284-186X
DOI
10.1080/0284186X.2023.2172688
language
English
LU publication?
yes
id
e687c1d0-3094-404c-bf72-92eabaadad67
date added to LUP
2023-03-08 09:22:24
date last changed
2024-06-13 12:55:56
@article{e687c1d0-3094-404c-bf72-92eabaadad67,
  abstract     = {{<p>Background: Soft tissue sarcomas are rare, morphologically, and genetically heterogenous. Though the tumors display abundant tumor stroma with infiltrating immune cells, the prognostic impact of various immunologic markers in sarcoma remains poorly defined. We aimed to characterize the immune landscape of a treatment-naïve cohort of soft tissue sarcoma of the extremities and the trunk wall with correlations to metastasis-free survival. Materials and Methods: We surveyed immunohistochemical expression patterns for CD163, CD20, CD3, CD8, and FOXP3 in 134 adult high-grade leiomyosarcomas, liposarcomas, and synovial sarcomas. Results: Macrophages outnumbered tumor-infiltrating lymphocytes. High CD163 infiltration was identified in 49% of the tumors and was overrepresented (66%) in leiomyosarcoma compared to liposarcoma (46%) and synovial sarcoma (9%). Tumor-grade also correlated with CD163 positivity with high expression in 53% of the high-grade lesions and 28% in low-grade tumors. Infiltrating CD3, CD8 and FOXP3-positive T-cells were significantly more prevalent in leiomyosarcomas than in liposarcomas/synovial sarcomas. CD20<sup>+</sup> B-cells were identified only in 14% of the STS. Correlation to established prognostic factors revealed a correlation between CD163<sup>+</sup> macrophages and necrosis and predicted an increased risk of metastases. No correlation between CD20<sup>+</sup> B-cells and known prognostic factors could be established, though CD20<sup>+</sup> B-cells infiltration predicted improved overall survival. Conclusion: We confirm that tumor-infiltrating macrophages outnumber tumor-infiltrating lymphocytes in soft tissue sarcoma and signify an increased risk of metastasis. CD20<sup>+</sup> B-cells are scarce in STS and correlate to improved survival. To date, immunotherapeutic strategies directed against T-cells have shown limited effect in soft tissue sarcoma. Our observations suggest that immunomodulatory agents focusing on macrophages may be worthwhile for further investigations in this tumor type. Further studies exploring the prognostic and predictive significance of CD20<sup>+</sup> B cells are warranted.</p>}},
  author       = {{Nyström, Helena and Jönsson, Mats and Nilbert, Mef and Carneiro, Ana}},
  issn         = {{0284-186X}},
  keywords     = {{cd163; cd20; sts; tam; tme}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{33--39}},
  publisher    = {{Taylor & Francis}},
  series       = {{Acta Oncologica}},
  title        = {{Immune-cell infiltration in high-grade soft tissue sarcomas; prognostic implications of tumor-associated macrophages and B-cells}},
  url          = {{http://dx.doi.org/10.1080/0284186X.2023.2172688}},
  doi          = {{10.1080/0284186X.2023.2172688}},
  volume       = {{62}},
  year         = {{2023}},
}