Publications by authors named "Zena Willsmore"
Article Synopsis
- Despite advancements in immunotherapies for melanoma, many patients still don't benefit due to current treatments mainly targeting T-cells rather than the more prevalent macrophages in the tumor environment.
- Macrophages have a dual role: they can activate the immune response and kill cancer cells, but they can also aid in tumor growth and spread depending on their interaction with the tumor microenvironment.
- A thorough understanding of macrophages' roles and interactions in melanoma, along with novel therapies aimed at them, is crucial for enhancing treatment outcomes for melanoma patients.
Article Synopsis
- - B cells play a crucial role in the immune response against tumors, particularly in melanoma, but their specific functions and characteristics have not been fully explored until now.
- - In this study, researchers found that memory B cells are more prevalent in tumors than in the bloodstream and exhibit unique antibody profiles that indicate processes like clonal expansion and affinity maturation.
- - The presence of tumor-associated B cells with autoimmune-like traits and high levels of antibodies related to both autoimmune diseases and cancer suggests a dysregulated immune response in melanoma patients.
The application of monoclonal antibodies (mAbs) for the treatment of melanoma has significantly improved the clinical management of this malignancy over the last decade. Currently approved mAbs for melanoma enhance T cell effector immune responses by blocking immune checkpoint molecules PD-L1/PD-1 and CTLA-4. However, more than half of patients do not benefit from treatment.
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- * In melanoma patients, TGF-β-expressing B cells form clusters in the tumor microenvironment and interact with T cells and regulatory T cells (Tregs) through specific signals, suggesting a complex relationship that can contribute to immune suppression.
- * The study highlights how B cells from melanoma patients may promote Treg differentiation and support T-helper cell functions, particularly when combined with anti-PD-1 treatment, indicating potential therapeutic implications for boosting anti-tumor immunity.
Article Synopsis
- Pembrolizumab, a checkpoint blocker, shows effective long-term responses in advanced non-small cell lung cancer but can lead to serious immune-related adverse events (irAEs) in some patients.
- The study highlights a deficiency in regulatory B cells, specifically those producing IL-10, which fails to control overly reactive T cell activity when PD-1/PD-L1 is inhibited, resulting in severe auto-inflammatory effects.
- The research suggests that profiling B cells before treatment could help identify lung cancer patients who are at a higher risk of experiencing severe irAEs during checkpoint blockade therapy.
BRAF inhibitors and their immunological effects in malignant melanoma.
Expert Rev Clin Immunol
April 2022
Article Synopsis
- - Recent advancements in melanoma treatment involve small-molecule inhibitors that target the MAPK pathway and immune checkpoint blockade, yet the 5-year survival rate for advanced cases is still about 50%.
- - The review focuses on how MAPK inhibitors, particularly BRAFi, affect the tumor microenvironment by changing inflammatory cytokine levels and immune cell activity, and considers potential treatment combinations.
- - Expert insights suggest that using MAPK inhibitors with existing therapies, like checkpoint inhibitors and adoptive cell therapies, could enhance immune responses and improve long-term patient outcomes in melanoma treatment.
Article Synopsis
- Primary cutaneous marginal zone B-cell lymphoma (MZL) is a slow-growing cancer characterized by a mix of B and T cells, particularly T follicular helper (TFH) cells, which have not been fully studied in this context.
- In a study involving biopsies from MZL and lymphoid hyperplasia cutis (LCH), researchers stained the samples to investigate the presence and levels of TFH markers such as Bcl-6 and PD-1.
- Results showed that both MZL and LCH contained TFH cells in low proportions, similar to those in reactive lymph nodes, suggesting a complex immune response rather than a straightforward malignancy classification.
Primary extramedullary plasmacytoma is rare monoclonal proliferation of plasma cells, which arise in various nonosseous anatomic locations without detectable underlying systemic disease. Historically, cutaneous infiltrates rich in mature neoplastic plasma cells have fallen into one of the following categories, plasmacytoma, lymphoplasmacytic lymphoma, and marginal zone lymphoma, which included immunocytoma. Since 2005, each of these was subsumed under the marginal zone lymphoma umbrella, largely on the basis of acknowledged diagnostic difficulties in some of these cases.
View Article and Find Full Text PDFThe contributions of the humoral immune response to melanoma are now widely recognized, with reports of positive prognostic value ascribed to tumor-infiltrating B cells (TIL-B) and increasing evidence of B cells as key predictors of patient response to treatment. There are disparate views as to the pro- and anti-tumor roles of B cells. B cells appear to play an integral role in forming tumor-associated tertiary lymphoid structures (TLSs) which can further modulate T cell activation.
View Article and Find Full Text PDFCytotoxic T-lymphocyte associated protein-4 (CTLA-4) and the Programmed Death Receptor 1 (PD-1) are immune checkpoint molecules that are well-established targets of antibody immunotherapies for the management of malignant melanoma. The monoclonal antibodies, Ipilimumab, Pembrolizumab, and Nivolumab, designed to interfere with T cell inhibitory signals to activate immune responses against tumors, were originally approved as monotherapy. Treatment with a combination of immune checkpoint inhibitors may improve outcomes compared to monotherapy in certain patient groups and these clinical benefits may be derived from unique immune mechanisms of action.
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