High tumor expression of CTLA4 identifies lymph node-negative basal-like breast cancer patients with excellent prognosis
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...
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Nature Portfolio
2025-06-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00865-z |
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| author | Andreas Hagen Røssevold Xavier Tekpli Ole Christian Lingjærde Hege G. Russnes Johan Vallon-Christersson Elin Borgen Jon Lømo Øystein Garred Esmaeil Dorraji Vessela N. Kristensen Bjørn Naume Jon Amund Kyte |
| author_facet | Andreas Hagen Røssevold Xavier Tekpli Ole Christian Lingjærde Hege G. Russnes Johan Vallon-Christersson Elin Borgen Jon Lømo Øystein Garred Esmaeil Dorraji Vessela N. Kristensen Bjørn Naume Jon Amund Kyte |
| author_sort | Andreas Hagen Røssevold |
| collection | DOAJ |
| description | 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 63rd percentile) is associated with an excellent prognosis in the Oslo1 cohort. None of the patients in the CTLA4 high 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/CTLA4 high 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. |
| format | Article |
| id | doaj-art-afdac54ef95a48fda1c87b56dd7d45a5 |
| institution | OA Journals |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-afdac54ef95a48fda1c87b56dd7d45a52025-08-20T02:37:35ZengNature PortfolioCommunications Medicine2730-664X2025-06-015111310.1038/s43856-025-00865-zHigh tumor expression of CTLA4 identifies lymph node-negative basal-like breast cancer patients with excellent prognosisAndreas Hagen Røssevold0Xavier Tekpli1Ole Christian Lingjærde2Hege G. Russnes3Johan Vallon-Christersson4Elin Borgen5Jon Lømo6Øystein Garred7Esmaeil Dorraji8Vessela N. Kristensen9Bjørn Naume10Jon Amund Kyte11Department of Clinical Cancer Research, Department of Oncology, Oslo University HospitalDepartment of Medical Genetics, Clinic for Laboratory Medicine, Oslo University HospitalDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University HospitalDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University HospitalDivision of Oncology, Department of Clinical Sciences Lund, Lund UniversityDepartment of Pathology, Oslo University HospitalDepartment of Pathology, Oslo University HospitalDepartment of Pathology, Oslo University HospitalDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University HospitalInstitute of Clinical Medicine, Faculty of Medicine, University of OsloInstitute of Clinical Medicine, Faculty of Medicine, University of OsloDepartment of Clinical Cancer Research, Department of Oncology, Oslo University HospitalAbstract 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 CTLA4 high 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/CTLA4 high 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.https://doi.org/10.1038/s43856-025-00865-z |
| spellingShingle | Andreas Hagen Røssevold Xavier Tekpli Ole Christian Lingjærde Hege G. Russnes Johan Vallon-Christersson Elin Borgen Jon Lømo Øystein Garred Esmaeil Dorraji Vessela N. Kristensen Bjørn Naume Jon Amund Kyte High tumor expression of CTLA4 identifies lymph node-negative basal-like breast cancer patients with excellent prognosis Communications Medicine |
| title | High tumor expression of CTLA4 identifies lymph node-negative basal-like breast cancer patients with excellent prognosis |
| title_full | High tumor expression of CTLA4 identifies lymph node-negative basal-like breast cancer patients with excellent prognosis |
| title_fullStr | High tumor expression of CTLA4 identifies lymph node-negative basal-like breast cancer patients with excellent prognosis |
| title_full_unstemmed | High tumor expression of CTLA4 identifies lymph node-negative basal-like breast cancer patients with excellent prognosis |
| title_short | High tumor expression of CTLA4 identifies lymph node-negative basal-like breast cancer patients with excellent prognosis |
| title_sort | high tumor expression of ctla4 identifies lymph node negative basal like breast cancer patients with excellent prognosis |
| url | https://doi.org/10.1038/s43856-025-00865-z |
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