Identification of tumor-reactive B cells and systemic IgG in breast cancer based on clonal frequency in the sentinel lymph node

AbstractA better understanding of antitumor immune responses is the key to advancing the field of cancer immunotherapy. Endogenous immunity in cancer patients, such as circulating anticancer antibodies or tumor-reactive B cells, has been historically yet incompletely described. Here, we demonstrate that tumor-draining (sentinel) lymph node (SN) is a rich source for tumor-reactive B cells that give rise to systemic IgG anticancer antibodies circulating in the bloodstream of breast cancer patients. Using a synergistic combination of high-throughput B-cell sequencing and quantitative immunoproteomics, we describe the prospective identification of tumor-reactive SN B cells (based on clonal frequency) and also demonstrate an unequivocal link between affinity-matured expanded B-cell clones in the SN and antitumor IgG in the blood. This technology could facilitate the discovery of antitumor antibody therapeutics and conceivably identify novel tumor antigens. Lastly, these findings highlight the unique and specialized niche the SN can fill in the advancement of cancer immunotherapy.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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This study identifies mechanisms mediating responses to immune checkpoint inhibitors using mouse models of triple-negative breast cancer. By creating new mammary tumor models, we find that tumor mutation burden and specific immune cells are associated with response. Further, we developed a rich resource of single-cell RNA-seq and bulk mRNA-seq data of immunotherapy-treated and non-treated tumors from sensitive and resistant murine models. Using this, we uncover that immune checkpoint therapy induces T follicular helper cell activation of B cells to facilitate the anti-tumor response in these models. We also show that B cel...
Source: Cell - Category: Cytology Source Type: research
(University of California - San Francisco) In a breakthrough with important implications for the future of immunotherapy for breast cancer, UC San Francisco scientists have found that blocking the activity of a single enzyme can prevent a common type of breast cancer from spreading to distant organs.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
AbstractIn the light of recent advances in the immunotherapy field for breast cancer (BC) treatment, especially in the triple‐negative subtype, the identification of reliable biomarkers capable of improving patient selection is paramount, because only a portion of patients seem to derive benefit from this appealing treatment strategy. In this context, the role of programmed cell death ligand 1 (PD‐L1) as a potential prognostic and/or predictive biomarker has been intensively explored, with controversial results. The aim of the present review is to collect available evidence on the biological relevance and clinical util...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Breast Cancer Source Type: research
AbstractPurpose of ReviewTo summarize and discuss the available evidence and ongoing efforts in order to establish the efficacy and safety of immunotherapeutic approaches in HER2-positive breast cancer.Recent FindingsThe introduction into the clinic of anti-HER2 –targeted therapies more than 15 years ago resulted in a substantial improvement in the outcome of patients with HER2-overexpressing breast cancer. However, only patients with the highest levels of HER2 expression will potentially benefit from these therapies and, unfortunately, many patients prog ress or relapse after optimal treatment. As metastatic breast ...
Source: Current Breast Cancer Reports - Category: Cancer & Oncology Source Type: research
Yicheng Ni Cancer remains a major cause of death globally. Given its relapsing and fatal features, curing cancer seems to be something hardly possible for the majority of patients. In view of the development in cancer therapies, this article summarizes currently available cancer therapeutics and cure potential by cancer type and stage at diagnosis, based on literature and database reviews. Currently common cancer therapeutics include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, treatment with curative intent by these methods are mainly eligible for patients with localized diseas...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
AbstractPurpose of ReviewImmune checkpoint blockade (ICB) has changed the clinical course of multiple cancer types and durable responses have now been observed in breast cancer (BC) patients. Most data suggest that, compared to other subtypes, triple-negative BC (TNBC) patients are more responsive to ICB, and anti-PD-L1 therapy is now approved in PD-L1+ metastatic TNBC, in combination with chemotherapy.Recent FindingsNearly 40% of PD-L1+ TNBC patients did not respond to this combination. Thus, additional biomarkers appear to be necessary to more precisely identify potential responders. A comprehensive analysis of the breas...
Source: Current Breast Cancer Reports - Category: Cancer & Oncology Source Type: research
Photodynamic therapy induces apoptosis and necrosis of 4T1 tumor cells, leading to the release of tumor ‐associated antigens. Matured dendritic cells migrate to the lymph node to activate T cells which infiltrate to the tumor cells. Small‐molecule inhibitor BMS‐202 acts through programmed death ligand 1 (PD‐L1) dimerization to block the activity of PD‐L1 proteins thus restoring T cell functi on. AbstractTargeting programmed cell death protein 1 (PD ‐1)/programmed death ligand 1 (PD‐L1) immunologic checkpoint blockade with monoclonal antibodies has achieved recent clinical success in antitumor therapy. However...
Source: Small - Category: Nanotechnology Authors: Tags: Communication Source Type: research
SummaryThe purpose of this observational study was to determine the prevalence of comorbid conditions in cancer patients with solid tumours selected for specific treatment at 12  divisions of medical oncology in Austria. Data from 1137 patients were collected using a standardized questionnaire; of these, 1036 datasets were evaluable for further analysis. Data were prospectively collected from patients during an in- or outpatient hospital visit over a 4-month period in 20 11. Of these patients 42% had gastrointestinal cancer, 31% had breast cancer, 9% lung cancer and the remaining had urogenital cancer, sarco...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 4 November 2019Source: Seminars in Cancer BiologyAuthor(s): Monica Benvenuto, Chiara Focaccetti, Valerio Izzi, Laura Masuelli, Andrea Modesti, Roberto BeiAbstractBreast cancer is both the most common type of cancer and the most frequent cause of cancer mortality in women, mainly because of its heterogeneity and limited immunogenicity. The aim of specific active cancer immunotherapy is to stimulate the host's immune response against cancer cells directly using a vaccine platform carrying one or more tumor antigens. In particular, the ideal tumor antigen should be able to elicit T cell and ...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Authors: Welslau M, Hartkopf AD, Müller V, Wöckel A, Lux MP, Janni W, Ettl J, Lüftner D, Belleville E, Schütz F, Fasching PA, Kolberg HC, Nabieva N, Overkamp F, Taran FA, Brucker SY, Wallwiener M, Tesch H, Schneeweiss A, Fehm TN Abstract Significant advancements have been made in recent years in advanced breast cancer and nearly all of them have been in the field of targeted therapy. Pertuzumab and trastuzumab-emtansine (T-DM1) have been able to be introduced in HER2-positive breast cancer. Now other anti-HER2 therapies are being developed (e.g. margetuximab, DS-8201a, pyrotinib) which can overc...
Source: Geburtshilfe und Frauenheilkunde - Category: OBGYN Tags: Geburtshilfe Frauenheilkd Source Type: research
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