Early Stage HER2-Positive Breast Cancers Not Achieving a pCR From Neoadjuvant Trastuzumab- or Pertuzumab-Based Regimens Have an Immunosuppressive Phenotype
| Autor: | Smita K. Nair, P. Kelly Marcom, Kimberly L. Blackwell, Terry Hyslop, Lynn Howie, Gloria Broadwater, Sara Abbott, Donna L. Topping, Jeremy Force, Michelle Parks, Kelly Westbrook, Gretchen Kimmick, Rex C. Bentley, Sarah Sammons, Ryan O. Emerson |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Adult Cancer Research medicine.medical_specialty Regulatory T cell H&E stain Breast Neoplasms Antibodies Monoclonal Humanized 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Antineoplastic Agents Immunological Lymphocytes Tumor-Infiltrating Trastuzumab Internal medicine Antineoplastic Combined Chemotherapy Protocols Immune Tolerance Tumor Microenvironment Medicine Humans Aged business.industry FOXP3 Middle Aged medicine.disease Carboplatin Neoadjuvant Therapy 030104 developmental biology medicine.anatomical_structure Docetaxel chemistry Chemotherapy Adjuvant 030220 oncology & carcinogenesis Female Pertuzumab business medicine.drug |
| Zdroj: | Clinical breast cancer. 18(5) |
| ISSN: | 1938-0666 |
| Popis: | Background Stromal tumor-infiltrating lymphocytes (TILs) might predict pathologic complete response (pCR) in patients with HER2-positive (HER2+) breast cancer treated with trastuzumab (H). Docetaxel (T), carboplatin (C), H, and pertuzumab (P) have immune-modulating effects. Pre- and post-treatment immune biomarkers in cancers treated with neoadjuvant TCH with or without P are lacking. In this study we quantified baseline and changes in TILs, cluster of differentiation (CD) 4+, CD8+, FoxP3+, and PD-L1+ cells using immunohistochemistry (IHC) and quantified productive T-cell receptor β (TCRβ) rearrangements and TCRβ clonality using next-generation sequencing (NGS) in 30 HER2+ breast cancer tissues treated with neoadjuvant H with or without P regimens. Materials and Methods Thirty pre- and post-neoadjuvant TCH (n = 4) or TCHP (n = 26) breast cancer tissues were identified. TILs were quantified manually using hematoxylin and eosin. CD4, CD8, FoxP3, and PD-L1 were stained using IHC. TCRβ was evaluated using NGS. Immune infiltrates were compared between pCR and non-pCR groups using the Wilcoxon rank sum test. Results A pCR occurred in 15 (n = 15; 50%) cancers (TCH n = 2; TCHP, n = 13). Pretreatment TILs, CD4+, CD8+, FoxP3+, and PD-L1+ cells were not associated with response (P = .42, P = .55, P = .19, P = .66, P = .87, respectively. Pretreatment productive TCRβ and TCRβ clonality did not predict response, P = .84 and P = .40, respectively). However, post-treatment CD4+ and FoxP3+ cells (T-regulatory cells) were elevated in the non-pCR cohort (P = .042 and P = .082, respectively). Conclusion An increase in regulatory T cells in non-pCR tissues suggests the development of an immunosuppressive phenotype. Further investigation in a larger cohort of samples is warranted to validate these findings. |
| Databáze: | OpenAIRE |
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