Histological subtype is associated with PD-L1 expression and CD8+ T-cell infiltrates in triple-negative breast carcinoma |
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| Institution: | 1. Department of Pathology, British Columbia Cancer Vancouver Centre, Vancouver, BC, Canada;2. University of British Columbia, Vancouver, BC, Canada;3. Department of Pathology, Royal Jubilee Hospital, Victoria, BC, Canada;1. Department of Pathology & Laboratory Medicine, Danbury Hospital Nuvance Health, Danbury, CT, USA;2. Department of Research and Innovation, Danbury Hospital Nuvance Health, Danbury, CT, USA;3. Breast Surgery, Helen F Graham Cancer Center, Newark, DE, USA;1. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States of America;2. Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America;3. Department of Medicine, University of Washington, Seattle, WA, United States of America;1. Department of Patology, Instituto Nacional de Cancerologia, Mexico;2. Department of Pathology, Hospital de Oncología, CMN SXII IMSS, Mexico;3. Department of Gynecology, Instituto Nacional de Cancerologia, Mexico;4. Biomedical Cancer Research Unit, Instituto Nacional de Cancerología, Mexico;5. Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico;1. Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands;2. Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands;3. Department of Pathology, Erasmus MC, Rotterdam, the Netherlands;4. Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands;5. Department of Radiology & Nuclear Medicine, Erasmus MC Cancer Institute, Rotterdam, the Netherlands;1. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA;2. GnomeDX, Powell, OH, USA;3. Rutgers University Hospital Department of Pathology, Newark, NY, USA;4. The Ohio State University Wexner Medical Center, Department of Anesthesiology, College of Medicine, Columbus, OH, USA;5. BioPerox-IL, Faculté des Sciences Gabriel, Université de Bourgogne-Franche Comté, Dijon, France |
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| Abstract: | Assessment of programmed death-ligand 1 (PD-L1) expression and CD8+ lymphocyte infiltrates in triple-negative breast carcinoma (TNBC) can provide valuable prognostic and predictive information. Knowledge of clinical and pathological factors that predict the status of these two markers is needed to better select patients likely to respond to immunotherapy. We aim to assess the association between histological subtypes of TNBC and tumor microenvironment type, defined here as each tumor's PD-L1 status and the percentage of CD8+ cells in its tumor-associated lymphocyte population. Tissue microarrays consisting of 72 TNBC cases (28 conventional invasive ductal carcinomas (IDCs), 21 basal-like IDCs, 18 apocrine carcinomas, and five metaplastic carcinomas) were evaluated for PD-L1 expression using the SP142 and 22C3 immunohistochemical (IHC) assays. The percentages of CD8+ and CD4+ intra-tumoral stromal lymphocytes in each case were analyzed using QuPath (open-source software platform) on CD8 and CD4 IHC-stained digital slides of the TMAs. Tumor-infiltrating lymphocytes (TILs) were also assessed on representative H&E-stained whole-tissue sections and compared to CD8+ and CD4+ lymphocyte percentages, and to the CD4/CD8 ratio of intra-tumoral lymphocytes for each case. Cases were then separated into four tumor microenvironment groups (PD-L1+/CD8+, PD-L1+/CD8-, PD-L1-/CD8+, and PD-L1-/CD8-). Basal-like IDCs were most often PD-L1-/CD8- (71.4%/61.9% of cases with SP142/22C3, respectively), while conventional IDCs were more distributed among PD-L1+ and PD-L1- microenvironments (35.7% PD-L1+/CD8+ and 42.9% PD-L1-/CD8- with the 22C3 assay). Apocrine carcinomas tended to be PD-L1-/CD8- (83.3% of cases with both SP142 and 22C3 antibodies). Metaplastic carcinomas were PD-L1-/CD8- in 60% of cases with both 22C3 and SP142. A CD8+ lymphocyte percentage ≥5% strongly predicted PD-L1 positivity (positive predictive value using the 22C3 assay: 0.75). Our data suggest that some histological subtypes of TNBC are predictive of PD-L1 status and CD8+ T-cell infiltrate levels. |
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