ABSTRACT
The EPICO (Spanish general registry of COVID-19 in children)-SEHOP (Spanish Society of Pediatric Hematology and Oncology) platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 14.7%), except in children with recent alloHSCT (less than 300 days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.
Subject(s)
COVID-19 , Comorbidity , Hematopoietic Stem Cell Transplantation , Neoplasms , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/complications , Child , Male , Adolescent , Female , Child, Preschool , Risk Factors , Neoplasms/epidemiology , Neoplasms/therapy , Infant , Spain/epidemiology , Registries , Transplantation, HomologousABSTRACT
One of the most used cephalosporins in clinical practice is cefuroxime axetil. Anaphylaxis due to the administration of cefuroxime is considered a rare event. We report a case of anaphylactic reaction after the administration of cefuroxime in a child who had tolerated the drug in past exposures. Diagnostic workup is recommended for all patients with at least a moderate anaphylactic reaction (hypotension, tachycardia, bronchial hyperreactivity). This should include a detailed history of the event, previous allergies, and underlying conditions. Unfortunately, all currently available diagnostic approaches (IgE, skin-prick-test, tryptase) leave a significant percentage of non-diagnostic results and false positive or negative outcomes.
Subject(s)
Anaphylaxis/chemically induced , Cefuroxime/analogs & derivatives , Cefuroxime/adverse effects , Cephalosporins/adverse effects , Child , Female , Humans , Skin Tests/methodsABSTRACT
Therapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4(+) T helper-1 (Th-1) lymphocytes, in addition to polarizing type-1 antitumor immune responses, impair tumor-induced CD4(+)CD25(+)FoxP3(+) regulatory T lymphocyte (Treg) immunosuppressive function in vitro and in vivo. Th-1 cells also inhibit the generation of FoxP3(+) Tregs from naive CD4(+)CD25(-)FoxP3(-) T cells by an interferon-γ-dependent mechanism. In addition, in an aggressive mouse leukemia model (12B1), Th-1 lymphocytes act synergistically with a chaperone-rich cell lysate (CRCL) vaccine, leading to improved survival and long-lasting protection against leukemia. The combination of CRCL as a source of tumor-specific antigens and Th-1 lymphocytes as an adjuvant has the potential to stimulate efficient specific antitumor immunity while restraining Treg-induced suppression.
Subject(s)
Cancer Vaccines/administration & dosage , Cell Extracts/administration & dosage , Forkhead Transcription Factors/metabolism , Immunologic Memory/immunology , Leukemia, Experimental/therapy , Molecular Chaperones/immunology , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Blotting, Western , Cancer Vaccines/immunology , Cell Extracts/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Interferon-gamma/metabolism , Leukemia, Experimental/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Nude , Mice, SCID , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Helper-Inducer/metabolism , T-Lymphocytes, Regulatory/metabolism , Tumor Cells, CulturedABSTRACT
We have previously reported on the anti-tumoral potential of a chaperone-rich cell lysate (CRCL) vaccine. Immunization with CRCL generated from tumors elicits specific T and NK cell-dependent immune responses leading to protective immunity in numerous mouse tumor models. CRCL provides both a source of tumor antigens and danger signals leading to dendritic cell activation. In humans, tumor-derived CRCL induces dendritic cell activation and CRCL-loaded dendritic cells promote the generation of cytotoxic T lymphocytes in vitro. The current study was designed to identify the signaling events and modifications triggered by CRCL in antigen presenting cells. Our results indicate that tumor-derived CRCL not only promotes the activation of dendritic cells, but also significantly fosters the function of macrophages that thus appear as major targets of this vaccine. Activation of both cell types is associated with the induction of the MAP kinase pathway, the phosphorylation of STAT1, STAT5 and AKT and with transcription factor NF-kappaB activation in vitro and in vivo. These results thus provide important insights into the mechanisms by which CRCL-based vaccines exert their adjuvant effects on antigen presenting cells.
