38feab5a5495fbc534112a84325e936f 264643.pdf 6c65689d97b83415a12c4372fa0d490946468736 264643.pdf be0ad4ec3bffa6610b701d9d10c390a7dfb2b8e3d1647f1e7817948e397a4d1c 264643.pdf Title: Effector Mechanisms of CD8+ HLA-DR+ T Cells in Breast Cancer Patients Who Respond to Neoadjuvant Chemotherapy Subject: Cytotoxic T lymphocyte (CTLs) activation is an independent predictor of response to neoadjuvant chemotherapy (NACT) in breast cancer (BC) patients. Here, we go deeper into the function of CD8+ HLA-DR+ T cells from NACT treated HER2 negative BC patients. Flow cytometry analysis revealed that CD8+ HLA-DR+ T cell percentage was increased in NACT responder (R) compared to non-responder (NR) patients. R patients with ER-/PR- hormone receptors had the highest CD8+ HLA-DR+ T cell frequencies, while no differences were found when patients were classified according to cancer stage or menopause status. Interestingly, the cytotoxicity and production of anti-tumor cytokines were enhanced when CD8+ HLA-DR+ T cells from healthy donors were cultured with plasma from R, but not from NR patients. The induced anti-tumor profile of CD8+ HLA-DR+ T cells was associated with plasmatic IL-12 and IFN- levels, increased cytokines in R patients. IL-12 or IFN- neutralization decreased cytotoxic activity and TNF- production by cultured CD8+ HLA-DR+ T cells in R plasma presence. All these data suggest that an effective response to NACT in BC patients is associated with increased IL-12 or IFN- levels involved in the induction of cytotoxic and pro-inflammatory mechanisms in CD8+ HLA-DR+ T cells. Keywords: breast cancer; CD8+ T cell; cytotoxicity Author: Rubén Osuna-Gómez, Cristina Arqueros, Carla Galano, Maria Mulet, Carlos Zamora, Agustí Barnadas and Silvia Vidal Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Dec 15 04:10:47 2021 CET ModDate: Wed Dec 15 04:42:35 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 18119073 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- GFKJOY+VnURWPalladioL Type 1 Custom yes yes no 10 0 MDJLZU+EURM10 Type 1 Builtin yes yes no 15 0 RVEZFM+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 FASCYM+URWPalladioL-Bold Type 1 Custom yes yes no 24 0 LMUVGP+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 XWOCXD+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 41 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 63 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 67 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 71 0 WTAUCZ+CMSY10 Type 1 Builtin yes yes no 86 0 GEWEQC+PazoMath-Italic Type 1 Builtin yes yes no 93 0 BIFICJ+PalatinoLinotype TrueType WinAnsi yes yes no 177 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:23:29 CEST RepresentationInformation: 264643.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 11:59:19 CEST Size: 18119073 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 367 FreeObjects: 13 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Method Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Patients and Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Surface Staining and Analysis by Flow Cytometry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Cell Culture and Intracellular Phenotyping by Flow Cytometry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Determination of Plasmatic Concentration of IL-12 and IFN- Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Statistics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: HLA-DR Expression on CD8+ T Cells Was Increased in R Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Plasma from R Patients Increased Cytotoxic and Pro-Inflammatory Activity of CD8+ HLA-DR+ T Cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Plasmatic Levels of IL-12 and IFN- Are Associated with Cytotoxic Activity on HLA-DR CD8+ T Cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Info: Title: Effector Mechanisms of CD8+ HLA-DR+ T Cells in Breast Cancer Patients Who Respond to Neoadjuvant Chemotherapy Author: Rubén Osuna-Gómez, Cristina Arqueros, Carla Galano, Maria Mulet, Carlos Zamora, Agustí Barnadas and Silvia Vidal Subject: Cytotoxic T lymphocyte (CTLs) activation is an independent predictor of response to neoadjuvant chemotherapy (NACT) in breast cancer (BC) patients. Here, we go deeper into the function of CD8+ HLA-DR+ T cells from NACT treated HER2 negative BC patients. Flow cytometry analysis revealed that CD8+ HLA-DR+ T cell percentage was increased in NACT responder (R) compared to non-responder (NR) patients. R patients with ER-/PR- hormone receptors had the highest CD8+ HLA-DR+ T cell frequencies, while no differences were found when patients were classified according to cancer stage or menopause status. Interestingly, the cytotoxicity and production of anti-tumor cytokines were enhanced when CD8+ HLA-DR+ T cells from healthy donors were cultured with plasma from R, but not from NR patients. The induced anti-tumor profile of CD8+ HLA-DR+ T cells was associated with plasmatic IL-12 and IFN- levels, increased cytokines in R patients. IL-12 or IFN- neutralization decreased cytotoxic activity and TNF- production by cultured CD8+ HLA-DR+ T cells in R plasma presence. All these data suggest that an effective response to NACT in BC patients is associated with increased IL-12 or IFN- levels involved in the induction of cytotoxic and pro-inflammatory mechanisms in CD8+ HLA-DR+ T cells. 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