Practical insights for regional multi-sectoral exercise planning: The Greater Toronto experience.

Exercise GTA Unified was a functional, multi-agency, cross-jurisdictional, health-sector focused mass casualty preparedness exercise conducted in the Greater Toronto Area (GTA) on 28th November, 2019. With over 1,000 unique paper-based and electronic injects and 34 participating agencies, including 22 separate hospital sites, Exercise GTA Unified is likely the largest health-sector focused mass casualty preparedness exercise ever conducted in Canada. The exercise design approach supported a successful, objective-based functional exercise, with elements of marked realism for participants.

Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes.

The tumor microenvironment (TME) represents a complex network between tumor cells and a variety of components including immune, stromal and vascular endothelial cells as well as the extracellular matrix. A wide panel of signals and interactions here take place, resulting in a bi-directional modulation of cellular functions. Many stimuli, on one hand, induce tumor growth and the spread of metastatic cells and, on the other hand, contribute to the establishment of an immunosuppressive environment.

Engineering the Bridge between Innate and Adaptive Immunity for Cancer Immunotherapy: Focus on γδ T and NK Cells.

Most studies on genetic engineering technologies for cancer immunotherapy based on allogeneic donors have focused on adaptive immunity. However, the main limitation of such approaches is that they can lead to severe graft-versus-host disease (GvHD). An alternative approach would bolster innate immunity by relying on the natural tropism of some subsets of the innate immune system, such as γδ T and natural killer (NK) cells, for the tumor microenvironment and their ability to kill in a major histocompatibility complex (MHC)-independent manner.

Preparedness planning and response to a mass-casualty incident: A case study of Sunnybrook Health Sciences Centre.

This case study describes a response to a real mass-casualty incident from the perspective of Sunnybrook Health Sciences Centre, a major trauma centre in Toronto, on a day when hospital occupancy levels were at a peak. To help evaluate the lessons learned from the incident response, the article also outlines the hospital's preparedness planning and the readiness assessment it conducted six months prior to the incident. Lessons learned from the readiness assessment are closely linked to those of the real incident, highlighting the importance of readiness assessments and that routine exercises are effective methods to identify opportunities for improvement and enhance preparedness.

Interleukin-30 Promotes Breast Cancer Growth and Progression.

The inflammatory tissue microenvironment that promotes the development of breast cancer is not fully understood. Here we report a role for elevated IL30 in supporting the breast cancer cell viability and invasive migration. IL30 was absent in normal mammary ducts, ductules, and acini of histologically normal breast and scanty in the few stromal infiltrating leukocytes.

The IMD innate immunity pathway of Drosophila influences somatic sex determination via regulation of the Doa locus.

The IMD pathway induces the innate immune response to infection by gram-negative bacteria. We demonstrate strong female-to-male sex transformations in double mutants of the IMD pathway in combination with Doa alleles. Doa encodes a protein kinase playing a central role in somatic sex determination through its regulation of alternative splicing of dsx transcripts.

γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes.

We prospectively assessed functional and phenotypic characteristics of γδ T lymphocytes up to 7 months after HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) depleted of αβ(+) T cells and CD19(+) B cells in 27 children with either malignant or nonmalignant disorders. We demonstrate that (1) γδ T cells are the predominant T-cell population in patients during the first weeks after transplantation, being mainly, albeit not only, derived from cells infused with the graft and expanding in vivo; (2) central-memory cells predominated very early posttransplantation for both Vδ1 and Vδ2 subsets; (3) Vδ1 cells are specifically expanded in patients experiencing cytomegalovirus reactivation and are more cytotoxic compared with those of children who did not experience reactivation; (4) these subsets display a cytotoxic phenotype and degranulate when challenged with primary acute myeloid and lymphoid leukemia blasts; and (5) Vδ2 cells are expanded in vitro after exposure to zoledronic acid (ZOL) and efficiently lyse primary lymphoid and myeloid blasts. This is the first detailed characterization of γδ T cells emerging in peripheral blood of children after CD19(+) B-cell and αβ(+) T-cell-depleted haplo-HSCT.

Failure of anti tumor-derived endothelial cell immunotherapy depends on augmentation of tumor hypoxia.

We have previously demonstrated that Tenascin-C (TNC)(+) human neuroblastoma (NB) cells transdifferentiate into tumor-derived endothelial cells (TDEC), which have been detected both in primary tumors and in tumors formed by human NB cell lines in immunodeficient mice. TDEC are genetically unstable and may favor tumor progression, suggesting that their elimination could reduce tumor growth and dissemination. So far, TDEC have never been targeted by antibody-mediated immunotherapy in any of the tumor models investigated.

Targeting acute myeloid leukemia cells with cytokines.

AML is a hematologic malignancy that represents 15-20% of all childhood acute leukemias and is responsible for more than one-half of pediatric leukemic deaths. The bulk tumor is continuously regenerated and sustained by rare leukemic ICs that proliferate slowly, thus resulting refractory to chemotherapeutic agents targeting highly proliferating cells within the tumor. Therefore, a complete eradication of the bulk tumor may depend on efficacy of therapies that target IC.

Interleukin-27 inhibits the growth of pediatric acute myeloid leukemia in NOD/SCID/Il2rg-/- mice.

Purpose: Acute myeloid leukemia (AML) accounts for more than half of fatal cases in all pediatric leukemia patients; this observation highlights the need of more effective therapies. Thus, we investigated whether interleukin (IL)-27, an immunomodulatory cytokine, functions as an antitumor agent against pediatric AML cells.

Experimental Design: Expression of WSX-1 and gp130 on AML cells from 16 pediatric patients was studied by flow cytometry.

Anti-leukemic properties of IL-12, IL-23 and IL-27: differences and similarities in the control of pediatric B acute lymphoblastic leukemia.

B acute lymphoblastic leukemia (ALL) is the most common pediatric hematologic malignancy. Although patient cure has reached an excellent rate, a minority of cases relapse and need novel therapies. IL-12, IL-23 and IL-27 belong to the IL-12 superfamily and exert immunological and anti-tumor functions.

Cytokines and microRNA in pediatric B-acute lymphoblastic leukemia.

B-acute lymphoblastic leukemia (ALL) is the most common hematologic tumor of pediatric age. Although patient survival has been improved, some cases still relapse and need alternative therapies. In this context, the role of microRNA in cancer is actually matter of investigation due to their regulatory function implicated in human tumorigenesis since the main target mRNA transcripts are involved in proliferation, apoptosis and differentiation.

Oct-4+/Tenascin C+ neuroblastoma cells serve as progenitors of tumor-derived endothelial cells.

Neuroblastoma (NB)-associated endothelial microvessels (EMs) may be lined by tumor-derived endothelial cells (TECs), that are genetically unstable and chemoresistant. Here we have addressed the identification of TEC progenitors in NB by focusing on Octamer-binding transcription factor 4 (Oct-4) as a putative marker. Oct-4(+) cells were detected in primary NB samples (n = 23), metastatic bone marrow aspirates (n = 10), NB cell lines (n = 4), and orthotopic tumors (n = 10) formed by the HTLA-230 NB cell line in immunodeficient mice.

Interleukin-27 and interleukin-23 modulate human plasmacell functions.

This study tested the hypothesis that IL-27 and IL-23, two heterodimeric cytokines involved in physiological immune responses and immunological disorders, may function on human PC and plasmablasts. It was reported that IL-27 acts on human mature B cells, but the role of IL-27 and IL-23 in human PC remains to be established. Thus, we have asked whether these cytokines may modulate human PC functions using human PPC generated in vitro, PC isolated from tonsils, and BM.

Direct inhibition of human acute myeloid leukemia cell growth by IL-12.

Acute myeloid leukemia is a haematopoietic malignancy originating from the transformation of myeloid progenitors that proliferate and accumulate in the bone marrow. In AML patients the survival rate at 5 years is 40-50% highlighting the need for novel therapies. In this study we have asked whether IL-12, an immuno-modulatory cytokine with anti-tumor activity, may inhibit directly AML cell growth.

Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells.

Interleukin (IL)-23 is a proinflammatory cytokine belonging to the IL-12 superfamily. The antitumor activity of IL-23 is controversial, and it is unknown whether or not the cytokine can act directly on tumor cells. The aim of this study was to investigate the potential direct antitumor activity of IL-23 in pediatric B-acute lymphoblastic leukemia (B-ALL) cells and to unravel the molecular mechanisms involved.

Interleukin-27 acts as multifunctional antitumor agent in multiple myeloma.

Purpose: Multiple myeloma (MM) derives from plasmablast/plasma cells that accumulate in the bone marrow. Different microenvironmental factors may promote metastatic dissemination especially to the skeleton, causing bone destruction. The balance between osteoclast and osteoblast activity represents a critical issue in bone remodeling.

Interleukin-12 receptor beta2: from cytokine receptor to gatekeeper gene in human B-cell malignancies.

Interleukin (IL) -12 is a cytokine that has been extensively characterized for its immunoregulatory activities. IL-12 binds to a heterodimeric receptor composed of the beta1 and beta2 chains. In this review article, we discuss recent findings on the expression and function of IL-12 receptor (IL-12R) in malignant B cells frozen at various stages of differentiation and in their normal counterparts.

IL-12 can target human lung adenocarcinoma cells and normal bronchial epithelial cells surrounding tumor lesions.

Background: Non small cell lung cancer (NSCLC) is a leading cause of cancer death. We have shown previously that IL-12rb2 KO mice develop spontaneously lung adenocarcinomas or bronchioalveolar carcinomas. Aim of the study was to investigate i) IL-12Rbeta2 expression in human primary lung adenocarcinomas and in their counterparts, i.

New perspectives for melanoma immunotherapy: role of IL-12.

Metastatic melanoma is a poor prognosis skin cancer. Since conventional treatments including surgery and chemotherapy often fail, novel therapeutic strategies are needed. In particular, identification of melanoma associated antigen has fostered the progress of both active (vaccines) and adoptive immunotherapy.

IL-21: a new player in the control of isotype switch in Peyer's patches.

Peyer's patches (PP) are lymphoid follicles of the small intestine containing predominantly IgA(+) B cells. In this JLB issue, IL-21 is reported to dampen TGF-beta1-induced IgG2b but not IgA production by mouse B cells, possibly explaining why IgA(+) B cells predominate in PP.