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Comparative analysis of malignant pleural effusion and peripheral blood reveals unique T cell signatures associated with survival in mesothelioma patients

The success of cancer immunotherapies has highlighted the importance of monitoring the anti-tumour T cell response. Patients with mesothelioma frequently present with a malignant pleural effusion (MPE) that is commonly drained regularly to alleviate symptoms. As MPE contains tumour cells, T cells and cytokines, it provides a unique opportunity to sample immune events at the tumour site.

Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma

Chemotherapy often kills a large fraction of cancer cells but leaves behind a small population of drug-tolerant persister cells. These persister cells survive drug treatments through reversible, non-genetic mechanisms and cause tumour recurrence upon cessation of therapy. Here, we report a drug tolerance mechanism regulated by the germ-cell-specific H3K4 methyltransferase PRDM9. 

Flt3L-mediated tumor cDC1 expansion enhances immunotherapy by priming stem-like CD8+ T cells in lymph nodes

Immune checkpoint blockade (ICB) evokes antitumor immunity through the reinvigoration of T cell responses. T cell differentiation status controls response, with less differentiated cells having an enhanced capacity to proliferate after ICB. Given that conventional type 1 dendritic cells (cDC1) maintain precursor exhausted T cells (TPEX), we hypothesized that expansion of cDC1s with Flt3L could enhance responses to ICB. 

Combining CRISPR-Cas9 and TCR exchange to generate a safe and efficient cord blood-derived T cell product for pediatric relapsed AML

Hematopoietic cell transplantation (HCT) is an effective treatment for pediatric patients with high-risk, refractory, or relapsed acute myeloid leukemia (AML). However, a large proportion of transplanted patients eventually die due to relapse. To improve overall survival, we propose a combined strategy based on cord blood (CB)-HCT with the application of AML-specific T cell receptor (TCR)-engineered T cell therapy derived from the same CB graft.

In their own words: advice from parents of children with cancer

Approximately 770 children are diagnosed with cancer in Australia every year. Research has explored their experiences and developed recommendations for improving support provided to families. These have included the provision of psychology services, improved communication between healthcare professionals and parents, and increased information for families. 

Vincristine Induced Adverse Effects in Lymphoma Bearing Dogs With Asymptomatic Neutropenia at the Time of Drug Administration

Vincristine sulphate, a microtubule inhibitor, is used extensively in veterinary oncology for treating lymphoma. Neutropenia during multiagent protocols is a common reason for treatment delay and reduced dose intensity. This study evaluated toxicities associated with treating systemically well neutropenic lymphoma patients with vincristine.

Disruption of cotranscriptional splicing suggests that RBM39 is a therapeutic target in acute lymphoblastic leukemia

There are few options for patients with relapse/refractory B-cell acute lymphoblastic leukemia, thus this is a major area of unmet medical need. Here, we reveal that inclusion of a poison exon in RBM39, which could be induced both by CDK9 or CDK9 independent CMGC (cyclin-dependent kinases, mitogen-activated protein kinases, glycogen synthase kinases, CDC-like kinases) kinase inhibition, is recognized by the nonsense-mediated mRNA decay pathway for degradation.

Childhood leukaemia in Down's syndrome primed by blood-cell bias

An in-depth investigation of gene regulation and cell populations at sites of fetal blood-cell production provides clues as to why children with Down’s syndrome are predisposed to developing leukaemia.

Exploiting temporal aspects of cancer immunotherapy

Many mechanisms underlying an effective immunotherapy-induced antitumour response are transient and critically time dependent. This is equally true for several immunological events in the tumour microenvironment induced by other cancer treatments. Immune checkpoint therapy (ICT) has proven to be very effective in the treatment of some cancers, but unfortunately, with many cancer types, most patients do not experience a benefit. 

New treatments on horizon for rarest child brain cancers

The WA Kids Cancer Centre has a suite of world-leading research projects to unlock new treatments for childhood cancers.