Clin Cancer Res
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Purpose: We profiled circulating tumor cells (CTCs) to study the biology of blood-borne metastasis and to monitor biomarker status in metastatic breast cancer (MBC). Methods: CTCs were isolated from 105 patients with MBC using EPCAM-based immunomagnetic enrichment and fluorescence-activated cells sorting (IE/FACS), 28 of whom had serial CTC analysis (74 samples, 2-5 time points). CTCs were subjected to microfluidic-based multiplex QPCR array of 64 cancer-related genes (n = 151) and genome-wide copy-number analysis by array comparative genomic hybridization (aCGH; n = 49). ⋯ Patients who harbored CTCs with high proliferation (MKI67) status had significantly reduced progression-free survival (P = 0.0011) and overall survival (P = 0.0095) compared with patients with low proliferative CTCs. Conclusions: We demonstrate an approach for complete isolation of EPCAM-positive CTCs and downstream comprehensive transcriptional/genomic characterization to examine the biology and assess breast cancer biomarkers in these cells over time. Clin Cancer Res; 24(6); 1486-99. ©2018 AACR.
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Immune checkpoint blockade has driven a revolution in modern oncology, and robust drug development of immune checkpoint inhibitors is underway in both solid tumors and hematologic malignancies. High response rates to programmed cell death 1 (PD-1) blockade using nivolumab or pembrolizumab in classical Hodgkin lymphoma (cHL) and several variants of non-Hodgkin lymphoma (NHL) revealed an intrinsic biological sensitivity to this approach, and work is ongoing exploring combinations with immune checkpoint inhibitors in both cHL and NHL. There are also preliminary data suggesting antitumor efficacy of PD-1 inhibitors used in combination with immunomodulatory drugs in multiple myeloma, and effects of novel monoclonal antibody therapies on the tumor microenvironment may lead to synergy with checkpoint blockade. ⋯ An important safety signal has emerged surrounding the risk of graft-versus-host disease associated with use of PD-1 inhibitors before and after allogeneic stem cell transplant. We aim to discuss the facts known to date in the use of immune checkpoint inhibitors for patients with lymphoid malignancies and our hopes for expanding the benefits of immunotherapy to patients in the future. Clin Cancer Res; 24(5); 1002-10. ©2017 AACR.