Clonal hematopoiesis of indeterminate potential is associated with increased risk of immune checkpoint inhibitor myocarditis in a prospective study of a cardio-oncology cohort.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to increase all-cause mortality and risk of cardiomyopathy in patients with solid malignancies. CHIP has also been shown to increase T cell activation in heart failure patients. It is unclear whether CHIP can affect the risk of immune checkpoint inhibitor (ICI) myocarditis in patients with cancer treated with immunotherapy.

Obesity induces PD-1 on macrophages to suppress anti-tumour immunity.

Obesity is a leading risk factor for progression and metastasis of many cancers, yet can in some cases enhance survival and responses to immune checkpoint blockade therapies, including anti-PD-1, which targets PD-1 (encoded by PDCD1), an inhibitory receptor expressed on immune cells. Although obesity promotes chronic inflammation, the role of the immune system in the obesity-cancer connection and immunotherapy remains unclear. It has been shown that in addition to T cells, macrophages can express PD-1.

Monoclonal antibodies as COVID-19 prophylaxis therapy in immunocompromised patient populations.

Objectives: The objective of this review was to examine the latest literature regarding the effectiveness of monoclonal antibodies as COVID-19 prophylaxis therapy for immunocompromised patient populations.

Methods: Literature review of published real-world and randomized control trials (RCTs) from 2020 to May 2023.

Results: COVID-19 is highly transmissible with potentially serious health outcomes, underscoring the need for effective prevention and treatment strategies.

SHP-2 and PD-1-SHP-2 signaling regulate myeloid cell differentiation and antitumor responses.

The inhibitory receptor PD-1 suppresses T cell activation by recruiting the phosphatase SHP-2. However, mice with a T-cell-specific deletion of SHP-2 do not have improved antitumor immunity. Here we showed that mice with conditional targeting of SHP-2 in myeloid cells, but not in T cells, had diminished tumor growth.

Immune cellular components and signaling pathways in the tumor microenvironment.

During the past decade there has been a revolution in cancer therapeutics by the emergence of antibody-based and cell-based immunotherapies that modulate immune responses against tumors. These new therapies have extended and improved the therapeutic efficacy of chemo-radiotherapy and have offered treatment options to patients who are no longer responding to these classic anti-cancer treatments. Unfortunately, tumor eradication and long-lasting responses are observed in a small fraction of patients, whereas the majority of patients respond only transiently.

The complex role of tumor-infiltrating macrophages.

Long recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being re-discovered as regulators of several diseases, including cancer. Tumor-associated macrophages (TAMs) represent the most abundant innate immune population in the tumor microenvironment (TME). Macrophages are professional phagocytic cells of the hematopoietic system specializing in the detection, phagocytosis and destruction of bacteria and other harmful micro-organisms, apoptotic cells and metabolic byproducts.

A Canadian Perspective: Monoclonal Antibodies for Pre- and Post-Exposure Protection from COVID-19 in Vulnerable Patients with Hematological Malignancies.

Patients with hematological malignancies have an increased risk of serious outcomes following COVID-19 infection, suggesting broader protection is needed beyond vaccination. Monoclonal antibodies such as sotrovimab, casirivimab-imdevimab, and bamlanivimab have provided valuable options for the treatment of COVID-19 disease. More recently, monoclonal antibodies have been examined for the prevention of COVID-19 infection.

Optimized Droplet Digital PCR Assay on Cell-Free DNA Samples for Non-Invasive Prenatal Diagnosis: Application to Beta-Thalassemia.

Background: Thalassemias are inherited blood disorders and by far one of the most common monogenic diseases globally. Beta-thalassemia has a particularly high prevalence in Cyprus, with the IVSI-110 G>A (HBB:c.93-21G>A) pathogenic variation representing almost 79% of the total carriers.

Single-cell RNA sequencing reveals evolution of immune landscape during glioblastoma progression.

Glioblastoma (GBM) is an incurable primary malignant brain cancer hallmarked with a substantial protumorigenic immune component. Knowledge of the GBM immune microenvironment during tumor evolution and standard of care treatments is limited. Using single-cell transcriptomics and flow cytometry, we unveiled large-scale comprehensive longitudinal changes in immune cell composition throughout tumor progression in an epidermal growth factor receptor-driven genetic mouse GBM model.

Novel Therapies for the Treatment of HER2-Positive Advanced Breast Cancer: A Canadian Perspective.

The advent of anti-HER2 targeted therapies has dramatically improved the outcome of HER2-positive breast cancer; however, resistance to treatment in the metastatic setting remains a challenge, highlighting the need for novel therapies. The arrival of new treatment options and clinical trials examining the efficacy of novel agents may improve outcomes in the metastatic setting, including in patients with brain metastases. In the first-line setting, we can potentially cure a selected number of patients treated with pertuzumab + trastuzumab + taxane.

Flow Cytometric Analysis for Identification of the Innate and Adaptive Immune Cells of Murine Lung.

The respiratory tract is in direct contact with the outside environment and requires a precisely regulated immune system to provide protection while suppressing unwanted reactions to environmental antigens. Lungs host several populations of innate and adaptive immune cells that provide immune surveillance but also mediate protective immune responses. These cells, which keep the healthy pulmonary immune system in balance, also participate in several pathological conditions such as asthma, infections, autoimmune diseases, and cancer.

Commentary on: Combination of Metabolic Intervention and T Cell Therapy Enhances Solid Tumor Immunotherapy.

Metabolism is a common cellular feature. Cancer creates a suppressive microenvironment resulting in inactivation of antigen-specific T cells by metabolic reprogramming. Development of approaches that enhance and sustain physiologic properties of T cell metabolism to prevent T cell inactivation and promote effector function in the tumor microenvironment is an urgent need for improvement of cell-based cancer immunotherapies.

A Canadian Perspective on the Challenges for Delivery of Curative-Intent Therapy in Stage III Unresectable Non-Small Cell Lung Cancer.

Stage III non-small cell lung cancer (NSCLC) comprises a highly heterogenous group of patients with regards to patient fitness and tumour size and distribution, resulting in a wide range of treatment goals and therapy options. Curative-intent multimodality treatment should be considered in all patients with stage III NSCLC. For patients with unresectable disease who are fit, have adequate lung function, and have a disease that can be encompassed within a radical radiation volume, concurrent chemoradiation therapy (cCRT) is the standard of care and can produce cure rates of 20-30%.

Bruton tyrosine kinase inhibitors for the frontline treatment of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (cll) is the most commonly diagnosed adult leukemia in Canada. Biologic heterogeneity of cll between patients results in variable disease trajectories and responses to therapy. Notably, compared with patients lacking high-risk features, those with such features-such as deletions in chromosome 17p, aberrations in the gene, or unmutated immunoglobulin heavy chain variable region genes-experience inferior outcomes and responses to standard chemoimmunotherapy.

Canadian perspective on managing multiple myeloma during the COVID-19 pandemic: lessons learned and future considerations.

The coronavirus disease 2019 (covid-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 has necessitated changes to the way patients with chronic diseases are managed. Given that patients with multiple myeloma are at increased risk of covid-19 infection and related complications, national bodies and experts around the globe have made recommendations for risk mitigation strategies for those vulnerable patients. Understandably, because of the novelty of the virus, many of the proposed risk mitigation strategies have thus far been reactionary and cannot be supported by strong evidence.

Highlights from ASCO 2020: updates on the treatment of chronic lymphocytic leukemia.

Because of the global coronavirus pandemic, the 2020 annual scientific meeting of the American Society of Clinical Oncology took place virtually, 29-30 May. At the meeting, results from key studies about the treatment of chronic lymphocytic leukemia (cll) were disseminated. Studies examined the efficacy and safety of ibrutinib, acalabrutinib, zanubrutinib, and venetoclax as monotherapy or in combination with novel agents for patients with treatment-naïve and relapsed or refractory cll.

The role of peroxisome proliferator-activated receptors (PPAR) in immune responses.

Peroxisome proliferator-activated receptors (PPARs) are fatty acid-activated transcription factors of nuclear hormone receptor superfamily that regulate energy metabolism. Currently, three PPAR subtypes have been identified: PPARα, PPARγ, and PPARβ/δ. PPARα and PPARδ are highly expressed in oxidative tissues and regulate genes involved in substrate delivery and oxidative phosphorylation (OXPHOS) and regulation of energy homeostasis.

Management of chronic lymphocytic leukemia in Canada during the coronavirus pandemic.

The emergence of the covid-19 disease pandemic caused by the 2019 novel coronavirus has required a re-evaluation of treatment practices for clinicians caring for patients with chronic lymphocytic leukemia (cll). The American Society for Hematology (ash) has provided a series of recommendations for the treatment of patients with cll during the pandemic, covering a range of topics, including testing for covid-19, cll treatment initiation and selection, use of immunoglobulin therapy, in-person monitoring, and treatment of patients with cll and covid-19. We summarize the ash recommendations and discuss their applicability as guidelines for the treatment of cll during the covid-19 pandemic in Canada.

Updates from the American Society of Hematology 2019 annual meeting: practice-changing studies in treatment-naïve chronic lymphocytic leukemia.

The 2019 annual meeting of the American Society of Hematology took place 7-10 December in Orlando, Florida. At the meeting, results from key studies in treatment-naïve chronic lymphocytic leukemia (cll) were presented. Of those studies, phase iii oral presentations focused on the efficacy and safety of therapy with inhibitors of Bruton tyrosine kinase (btk) and Bcl-2.

Update on the subcutaneous administration of rituximab in Canadian cancer centres.

Results of studies comparing subcutaneous (sc) with intravenous (iv) rituximab indicate that the two formulations are comparable in efficacy, but most patients and health care professionals prefer the sc route, commonly because of shorter chair time and reduced risk of infusion-related reactions. Recent Canadian data, including those from the scuba study reported here, support the results of earlier international studies showing a reduction in preparation and administration time with the sc formulation, lower cost of administration, and reduced drug wastage because of the fixed sc dosing. Given the significant time and cost savings of the sc formulation, that formulation is generally preferred over the iv formulation for the treatment of follicular lymphoma, diffuse large B cell lymphoma, and chronic lymphocytic leukemia.

Targeted deletion of PD-1 in myeloid cells induces antitumor immunity.

PD-1, a T cell checkpoint receptor and target of cancer immunotherapy, is also expressed on myeloid cells. The role of myeloid-specific versus T cell-specific PD-1 ablation on antitumor immunity has remained unclear because most studies have used either PD-1-blocking antibodies or complete PD-1 KO mice. We generated a conditional allele, which allowed myeloid-specific (PD-1) or T cell-specific (PD-1) targeting of gene.