Pinho et al. detected circulating tumor-reactive CD8+ T cell responses in the blood of patients with early-stage HR+ breast cancer by ex vivo stimulation. Circulating tumor-reactive T cells were cytotoxic, showed diverse TCR clonotypes, and some reacted to known cancer testes antigens. The presence of circulating tumor-reactive T cell responses correlated with CD8+ T cell infiltration. Patients with lymph node metastases either lacked or had a significantly lower proportions of tumor-reactive TILs. Patients with lymph node-positive HR+ breast cancer also showed lower frequencies of intratumoral neoantigen-specific CD8+ T cells in two independent scRNAseq datasets.
Contributed by Shishir Pant
ABSTRACT: Most breast cancers express the estrogen receptor (ER), but the immune response of hormone receptor-positive (HR(+)) breast cancer remains poorly characterized. Here, dendritic cells loaded with tumor lysate are used to identify tumor-reactive CD8 T cells, which are detected in most HR(+) breast cancer patients, especially those with early-stage tumors. When present, the circulating antitumor CD8 response contains cytotoxic T cells with diverse specificity and T cell receptor (TCR) repertoire. Additionally, patients with blood cancer-specific T cells have significantly more CD8 tumor-infiltrating lymphocytes (TILs). Moreover, tumor-reactive TCR sequences are detected in the tumor, but at a significantly lower proportion in patients with lymph node involvement. Our data suggest that HR(+) breast cancer patients with lymph node metastasis lack tumor-specific CD8 T cells with capacity to infiltrate the tumor at significant levels. However, early-stage patients have a diverse antitumor CD8 response that could be harnessed to develop immunotherapeutic approaches for late-stage HR(+) patients.
Author Info: (1) Medical Research Council Translational Immune Discovery Unit (MRC TIDU), Weatherall Institute of Molecular Medicine (WIMM), University of Oxford, Oxford, UK; Chinese Academy of
Author Info: (1) Medical Research Council Translational Immune Discovery Unit (MRC TIDU), Weatherall Institute of Molecular Medicine (WIMM), University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. (2) Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. (3) Medical Research Council Translational Immune Discovery Unit (MRC TIDU), Weatherall Institute of Molecular Medicine (WIMM), University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. (4) Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. (5) Medical Research Council Translational Immune Discovery Unit (MRC TIDU), Weatherall Institute of Molecular Medicine (WIMM), University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. (6) Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. (7) Medical Research Council Translational Immune Discovery Unit (MRC TIDU), Weatherall Institute of Molecular Medicine (WIMM), University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. (8) Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK. (9) Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. (10) Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK. (11) Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK. (12) Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK. (13) Department of Cellular Pathology, Oxford University NHS Foundation Trust, Oxford, UK. (14) Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK; Oxford National Institute of Health Research (NIHR) Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK. (15) Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK; Oxford National Institute of Health Research (NIHR) Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK. (16) Department of Oncology, University of Oxford, Oxford, UK. (17) Sequencing Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. (18) Flow Cytometry Facility, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. (19) Flow Cytometry Facility, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. (20) Flow Cytometry Facility, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. (21) Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. (22) Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. (23) Department of Oncology, University of Oxford, Oxford, UK. (24) Medical Research Council Translational Immune Discovery Unit (MRC TIDU), Weatherall Institute of Molecular Medicine (WIMM), University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. (25) Department of Breast Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. (26) Medical Research Council Translational Immune Discovery Unit (MRC TIDU), Weatherall Institute of Molecular Medicine (WIMM), University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Electronic address: tao.dong@ndm.ox.ac.uk.
