Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

High tumor expression of CTLA4 identifies lymph node-negative basal-like breast cancer patients with excellent prognosis

Røssevold, Andreas Hagen ; Tekpli, Xavier ; Lingjærde, Ole Christian ; Russnes, Hege G. ; Vallon-Christersson, Johan LU orcid ; Borgen, Elin ; Lømo, Jon ; Garred, Øystein ; Dorraji, Esmaeil and Kristensen, Vessela N. , et al. (2025) In Communications medicine 5(1).
Abstract

Background: Tumor immune cell infiltration is a favorable prognostic factor in triple-negative breast cancer. Most triple-negative tumors belong to the aggressive basal-like subtype. We hypothesized that immune gene expression may identify low-risk patients for whom adjuvant chemotherapy can be de-escalated. Methods: The expression of 753 immune-related genes was analyzed in tumor biopsies from 45 patients with basal-like disease and no lymph node metastases (Oslo1 cohort) and evaluated for prognostic value. Findings were validated in two independent cohorts. Oslo1 biopsies were also analyzed for tumor-infiltrating lymphocytes (TIL) and tertiary lymphoid structures (TLS). Results: Here we show that a high expression of CTLA4 (above... (More)

Background: Tumor immune cell infiltration is a favorable prognostic factor in triple-negative breast cancer. Most triple-negative tumors belong to the aggressive basal-like subtype. We hypothesized that immune gene expression may identify low-risk patients for whom adjuvant chemotherapy can be de-escalated. Methods: The expression of 753 immune-related genes was analyzed in tumor biopsies from 45 patients with basal-like disease and no lymph node metastases (Oslo1 cohort) and evaluated for prognostic value. Findings were validated in two independent cohorts. Oslo1 biopsies were also analyzed for tumor-infiltrating lymphocytes (TIL) and tertiary lymphoid structures (TLS). Results: Here we show that a high expression of CTLA4 (above 63rd percentile) is associated with an excellent prognosis in the Oslo1 cohort. None of the patients in the CTLA4high group suffered disease recurrence (median follow-up 7.4 years) or breast cancer-related death (median follow-up 17.7 years). Analysis of the SCAN-B (n = 233; 97% without distant recurrence in CTLA4high group) and METABRIC cohorts (n = 155; 93% disease-specific survival in CTLA4high group) validates this finding, which also applies to patients who did not receive chemotherapy. CTLA4 expression correlates with TIL score and TLS levels (Oslo1 cohort), but no TILlow/CTLA4high patients died from breast cancer, suggesting that the CTLA4 readout identifies low-risk patients not captured by TIL assessment. Conclusions: A high primary tumor expression of CTLA4 identifies patients with an excellent prognosis, for whom standard chemotherapy may be de-escalated or omitted.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Communications medicine
volume
5
issue
1
article number
234
publisher
Nature Publishing Group
external identifiers
  • pmid:40523912
  • scopus:105008239040
ISSN
2730-664X
DOI
10.1038/s43856-025-00865-z
language
English
LU publication?
yes
id
379c74b1-7e13-4d3b-83f6-fb722a228983
date added to LUP
2025-10-27 09:50:37
date last changed
2025-11-24 12:25:37
@article{379c74b1-7e13-4d3b-83f6-fb722a228983,
  abstract     = {{<p>Background: Tumor immune cell infiltration is a favorable prognostic factor in triple-negative breast cancer. Most triple-negative tumors belong to the aggressive basal-like subtype. We hypothesized that immune gene expression may identify low-risk patients for whom adjuvant chemotherapy can be de-escalated. Methods: The expression of 753 immune-related genes was analyzed in tumor biopsies from 45 patients with basal-like disease and no lymph node metastases (Oslo1 cohort) and evaluated for prognostic value. Findings were validated in two independent cohorts. Oslo1 biopsies were also analyzed for tumor-infiltrating lymphocytes (TIL) and tertiary lymphoid structures (TLS). Results: Here we show that a high expression of CTLA4 (above 63<sup>rd</sup> percentile) is associated with an excellent prognosis in the Oslo1 cohort. None of the patients in the CTLA4<sup>high</sup> group suffered disease recurrence (median follow-up 7.4 years) or breast cancer-related death (median follow-up 17.7 years). Analysis of the SCAN-B (n = 233; 97% without distant recurrence in CTLA4<sup>high</sup> group) and METABRIC cohorts (n = 155; 93% disease-specific survival in CTLA4<sup>high</sup> group) validates this finding, which also applies to patients who did not receive chemotherapy. CTLA4 expression correlates with TIL score and TLS levels (Oslo1 cohort), but no TIL<sup>low</sup>/CTLA4<sup>high</sup> patients died from breast cancer, suggesting that the CTLA4 readout identifies low-risk patients not captured by TIL assessment. Conclusions: A high primary tumor expression of CTLA4 identifies patients with an excellent prognosis, for whom standard chemotherapy may be de-escalated or omitted.</p>}},
  author       = {{Røssevold, Andreas Hagen and Tekpli, Xavier and Lingjærde, Ole Christian and Russnes, Hege G. and Vallon-Christersson, Johan and Borgen, Elin and Lømo, Jon and Garred, Øystein and Dorraji, Esmaeil and Kristensen, Vessela N. and Naume, Bjørn and Kyte, Jon Amund}},
  issn         = {{2730-664X}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Communications medicine}},
  title        = {{High tumor expression of CTLA4 identifies lymph node-negative basal-like breast cancer patients with excellent prognosis}},
  url          = {{http://dx.doi.org/10.1038/s43856-025-00865-z}},
  doi          = {{10.1038/s43856-025-00865-z}},
  volume       = {{5}},
  year         = {{2025}},
}