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Effector memory cytotoxic CD3+/CD8+/CD45RO+ T cells are predictive of good survival and a lower risk of recurrence in triple-negative breast cancer.
Sun, Xiangjie; Zhai, Jie; Sun, Baohua; Parra, Edwin Roger; Jiang, Mei; Ma, Wencai; Wang, Jing; Kang, Anthony M; Kannan, Kasthuri; Pandurengan, Renganayaki; Zhang, Shanyu; Solis, Luisa Maren; Haymaker, Cara L; Raso, Maria Gabriela; Mendoza Perez, Julia; Sahin, Aysegul A; Wistuba, Ignacio I; Yam, Clinton; Litton, Jennifer K; Yang, Fei.
Affiliation
  • Sun X; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Zhai J; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Sun B; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Parra ER; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Jiang M; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Ma W; Bioinformatics & Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wang J; Bioinformatics & Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Kang AM; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Kannan K; Department of Computational and Applied Mathematics, Rice University, Houston, TX, USA.
  • Pandurengan R; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Zhang S; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Solis LM; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Haymaker CL; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Raso MG; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Mendoza Perez J; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Sahin AA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wistuba II; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Yam C; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Litton JK; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Yang F; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. jlitton@mdanderson.org.
Mod Pathol ; 35(5): 601-608, 2022 05.
Article in En | MEDLINE | ID: mdl-34839351
ABSTRACT
Triple-negative breast cancer (TNBC) with high tumour-infiltrating lymphocytes (TILs) has been associated with a promising prognosis. To better understand the prognostic value of immune cell subtypes in TNBC, we characterised TILs and the interaction between tumour cells and immune cell subtypes. A total of 145 breast cancer tissues were stained by multiplex immunofluorescence (mIF), including panel 1 (PD-L1, PD-1, CD3, CD8, CD68 and CK) and panel 2 (Foxp3, Granzyme B, CD45RO, CD3, CD8 and CK). Phenotypes were analysed and quantified by pathologists using InForm software. We found that in the ER-negative (ER <1% and HER2-negative) group and the ER/PR-low positive (ER 1-9% and HER2-negative) group, 11.2% and 7.1% of patients were PD-L1+ by the tumour cell score, 29.0% and 28.6% were PD-L1+ by the modified immune cell score and 30.8% and 32.1% were PD-L1+ by the combined positive score. We combined ER-negative and ER/PR-low positive cases for the survival analysis since a 10% cut-off is often used in clinical practice for therapeutic purposes. The densities of PD-L1+ tumour cells (HR 0.366, 95% CI 0.138-0.970; p = 0.043) within the tumour compartment and CD3+ immune cells in the total area (tumour and stromal compartments combined) (HR 0.213, 95% CI 0.070-0.642; p = 0.006) were favourable prognostic biomarkers for overall survival (OS) in TNBC. The density of effector/memory cytotoxic T cells (CD3+CD8+CD45RO+) in the tumour compartment was an independent prognostic biomarker for OS (HR 0.232, 95% CI 0.086-0.628; p = 0.004) and DFS (HR 0.183, 95% CI 0.1301-0.744; p = 0.009) in TNBC. Interestingly, spatial data suggested that patients with a higher density of PD-L1+ tumour cells had shorter cell-cell distances from tumour cells to cytotoxic T cells (p < 0.01). In conclusion, we found that phenotyping tumour immune cells by mIF is highly informative in understanding the immune microenvironment in TNBC. PD-L1+ tumour cells, total T cells and effector/memory cytotoxic T cells are promising prognostic biomarkers in TNBC.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Triple Negative Breast Neoplasms / Immunologic Memory Type of study: Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: Mod Pathol Journal subject: PATOLOGIA Year: 2022 Document type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Triple Negative Breast Neoplasms / Immunologic Memory Type of study: Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: Mod Pathol Journal subject: PATOLOGIA Year: 2022 Document type: Article Affiliation country: United States