Phillip K Darcy

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T cell shape is dictated by the selective recruitment of molecules to different regions of the cell (polarity) and is integral to every aspect of T cell function, from migration to cytotoxicity. This study describes a mechanism for the regulation of T cell polarity. We show that T cells contain a network of asymmetrically distributed proteins with the(More)
Using gene-expression data from over 6,000 breast cancer patients, we report herein that high CD73 expression is associated with a poor prognosis in triple-negative breast cancers (TNBC). Because anthracycline-based chemotherapy regimens are standard treatment for TNBC, we investigated the relationship between CD73 and anthracycline efficacy. In TNBC(More)
CD73 is a cell-surface enzyme that suppresses immune responses by producing extracellular adenosine. In this study, we employed CD73 gene-targeted mice to investigate the role of host-derived CD73 on antitumor immunity and tumor cell metastasis. We found that CD73 ablation significantly suppressed the growth of ovalbumin-expressing MC38 colon cancer, EG7(More)
Progression of colorectal cancer (CRC) involves spatial and temporal occurrences of epithelial-mesenchymal transition (EMT), whereby tumour cells acquire a more invasive and metastatic phenotype. Subsequently, the disseminated mesenchymal tumour cells must undergo a reverse transition (mesenchymal-epithelial transition, MET) at the site of metastases, as(More)
T cells have the capacity to eradicate diseased cells, but tumours present considerable challenges that render T cells ineffectual. Cancer cells often make themselves almost 'invisible' to the immune system, and they sculpt a microenvironment that suppresses T cell activity, survival and migration. Genetic engineering of T cells can be used therapeutically(More)
Mapping and complementation analysis with 17 phototaxis mutations has established 11 complementation groups phoA-phoK distributed over six linkage groups. Statistical calculations from the complementation data yielded 17 as the maximum likelihood estimate of the number of pho genes assuming all loci are equally mutable. Most of the phototaxis mutants were(More)
Natural killer (NK) cells are potent immune effector cells that can respond to infection and cancer, as well as allowing maternal adaptation to pregnancy. In response to malignant transformation or pathogenic invasion, NK cells can secrete cytokine and may be directly cytolytic, as well as exerting effects indirectly through other cells of the immune(More)
A new strategy to improve the therapeutic utility of redirected T cells for cancer involves the development of novel Ag-specific chimeric receptors capable of stimulating optimal and sustained T cell antitumor activity in vivo. Given that T cells require both primary and costimulatory signals for optimal activation and that many tumors do not express(More)
The immune system plays a critical role in the elimination and suppression of pathogens. Although the endogenous immune system is capable of immune surveillance resulting in the elimination of cancer cells, tumor cells have developed a variety of mechanisms to escape immune recognition often resulting in tumor outgrowth. The presence of immune infiltrate in(More)
Natural killer (NK) cells may modulate the development of adaptive immune responses, but until now there has been little evidence to support this hypothesis. We investigated the primary and secondary immunity elicited by various tumor cell lines that express CD70 and interact with CD70 ligand (CD27), which is constitutively expressed on NK cells. CD70(More)