ArticleBreast cancer research : BCR2019
Comprehensive evaluation of methods to assess overall and cell-specific immune infiltrates in breast cancer.
Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Association between cumulative lifetime exposure to reproductive hormones and tumor-infiltrating lymphocytes, CD4 +, and CD8 + T cells among women with breast cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Huaier Polysaccharides Sensitize Anti-PD-L1 Therapy via Promoting Antitumor Immune Response in Triple-Negative Breast Cancer.International journal of biological sciences · 2026Article
- Expression of ITGA3 in pan-cancer tissues and its relationship to prognosis and immune infiltration.Discover oncology · 2025Article
- Interobserver concordance of tumor-infiltrating lymphocyte assessment in triple-negative breast carcinoma; tissue microarray versus whole sections.CytoJournal · 2025Article
- Tumour immune characterisation of primary triple-negative breast cancer using automated image quantification of immunohistochemistry-stained immune cells.Scientific reports · 2024Article
- Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer.The Journal of pathology · 2024Review
- Converging and evolving immuno-genomic routes toward immune escape in breast cancer.Nature communications · 2024Article
- The Value of Tumor Infiltrating Lymphocytes (TIL) for Predicting the Response to Neoadjuvant Chemotherapy (NAC) in Breast Cancer according to the Molecular Subtypes.Biomedicines · 2023Article
- B-cells and regulatory T-cells in the microenvironment of HER2+ breast cancer are associated with decreased survival: a real-world analysis of women with HER2+ metastatic breast cancer.Breast cancer research : BCR · 2023Article
- Obesity-associated changes in molecular biology of primary breast cancer.Nature communications · 2023Article
- Impact of immune infiltration signatures on prognosis in endometrial carcinoma is dependent on the underlying molecular subtype.Gynecologic oncology · 2023Article
- Combination of furosemide, gold, and dopamine as a potential therapy for breast cancer.Functional & integrative genomics · 2023Article
- Spatial interplay of lymphocytes and fibroblasts in estrogen receptor-positive HER2-negative breast cancer.NPJ breast cancer · 2022Article
- Spatial Characterization of Tumor-Infiltrating Lymphocytes and Breast Cancer Progression.Cancers · 2022Article
- Dissecting Tumor-Immune Microenvironment in Breast Cancer at a Spatial and Multiplex Resolution.Cancers · 2022Review
- Review
- Differential effects of CD20+ B cells and PD-L1+ immune cells on pathologic complete response and outcome: comparison between inflammatory breast cancer and locally advanced breast cancer patients.Breast cancer research and treatment · 2021Article
- The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group.NPJ breast cancer · 2021Review
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Authors and funding
21 authors at 10 institutions in 5 countries.
Funding
Abstract
backgroundBreast cancer (BC) immune infiltrates play a critical role in tumor progression and response to treatment. Besides stromal tumor infiltrating lymphocytes (sTILs) which have recently reached level 1B evidence as a prognostic marker in triple negative BC, a plethora of methods to assess immune infiltration exists, and it is unclear how these compare to each other and if they can be used interchangeably.
methodsTwo experienced pathologists scored sTIL, intra-tumoral TIL (itTIL), and 6 immune cell types (CD3
resultsThe concordance correlation coefficient (CCC) between pathologists for sTIL was very good (0.84) and for cell-specific immune infiltrates slightly lower (0.63-0.66). Comparison between tissue microarray and whole slide pathology scores revealed systematically higher values in whole slides (ratio 2.60-5.98). The Spearman correlations between microscopic sTIL and transcriptomic- or methylomic-based assessment of immune infiltrates were highly variable (r = 0.01-0.56). Similar observations were made for cell type-specific quantifications (r = 0.001-0.54). We observed a strong inter-method variability between the omics-derived estimations, which is further cell type dependent. Finally, we demonstrated that most methods more accurately identify highly infiltrated (sTIL ≥ 60%; area under the curve, AUC, 0.64-0.99) as compared to lowly infiltrated tumors (sTIL ≤ 10%; AUC 0.52-0.82).
conclusionsThere is a lower inter-pathologist concordance for cell-specific quantification as compared to overall infiltration quantification. Microscopic assessments are underestimated when considering small cores (tissue microarray) instead of whole slides. Results further highlight considerable differences between the microscopic-, transcriptomic-, and methylomic-based methods in the assessment of overall and cell-specific immune infiltration in BC. We therefore call for extreme caution when assessing immune infiltrates using current methods and emphasize the need for standardized immune characterization beyond TIL.
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