Publications by authors named "Marc D Macaluso"
Surgical removal of primary tumors was shown to reverse tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT)-containing treatments is not understood. Here, we report the first prospective, non-comparative clinical trial to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma (mccRCC).
View Article and Find Full Text PDFResistance to immune checkpoint therapy (ICT) presents a growing clinical challenge. The tumor microenvironment (TME) and its components, namely tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), play a pivotal role in ICT resistance; however, the underlying mechanisms remain under investigation. In this study, we identify expression of TNF-Stimulated Factor 6 (TSG-6) in ICT-resistant pancreatic tumors, compared to ICT-sensitive melanoma tumors, both in mouse and human.
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- Glioblastoma (GBM) tumors have a high presence of immune-suppressive myeloid cells, making them hard to treat with immune checkpoint therapy (ICT).
- Research shows that deleting the Kdm6b gene from these myeloid cells can boost pro-inflammatory pathways, improving survival rates in mice with GBM.
- Targeting the epigenetic enzyme KDM6B may enhance myeloid cell function and potentially improve the effectiveness of cancer immunotherapies.
Article Synopsis
- Immune checkpoint therapy, specifically anti-PD-L1 and anti-CTLA-4, is being explored as a neoadjuvant treatment for patients with localized urothelial carcinoma, particularly those unable to receive cisplatin.
- In a pilot trial, 28 patients with high-risk features (e.g., bulky tumors, variant histology) were treated, showing a pathological complete response rate of 37.5% and 58% downstaging to pT1 or less after surgery.
- Although 21% of patients experienced grade ≥3 immune-related adverse events, the findings suggest promising safety and efficacy, prompting further research in this patient population lacking established treatments.
15-Lipoxygenase-2 (15-LOX2) is a human-specific lipid-peroxidizing enzyme most prominently expressed in epithelial cells of normal human prostate but downregulated or completely lost in>70% of prostate cancer (PCa) cases. Transgenic expression of 15-LOX2 in the mouse prostate surprisingly causes hyperplasia. Here we first provide evidence that 15-LOX2-induced prostatic hyperplasia does not progress to PCa even in p53(+/-) or p53(-/-) background.
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