Alison M. McDonnell

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Tumors have evolved multiple mechanisms to evade immune destruction. One of these is expression of T cell inhibitory ligands such as programmed death-ligand 1 (PD-L1; B7-H1). In this study, we show that PD-L1 is highly expressed on mesothelioma tumor cells and within the tumor stroma. However, PD-L1 blockade only marginally affected tumor growth and was(More)
Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that are critical for the generation of effective cytotoxic T lymphocyte (CTL) responses; however, their function and phenotype are often defective or altered in tumor-bearing hosts, which may limit their capacity to mount an effective tumor-specific CTL response. In particular, the(More)
One of the clear paradoxes in tumor immunology is the fact that cross-presentation of cell-associated tumor antigens to CD8(+) T cells is efficient, yet CTL generation is weak, and tumors continue to grow. We examined, for the first time whether this may be due to alterations in the phenotype or function of cross-presenting DC using a solid tumor model(More)
BACKGROUND Data from murine models suggest that CD40 activation may synergize with cytotoxic chemotherapy. We aimed to determine the maximum tolerated dose (MTD) and toxicity profile and to explore immunological biomarkers of the CD40-activating antibody CP-870,893 with cisplatin and pemetrexed in patients with malignant pleural mesothelioma (MPM). (More)
The immune system plays an important role in the surveillance of neoplastic cells by eliminating them before they manifest as full-blown cancer. Despite this, tumors do develop in the presence of a functioning immune system. Conventional chemotherapy and its ability to directly kill tumor cells is one of the most effective weapons in the fight against(More)
Cross-presentation defines the unique capacity of an APC to present exogenous Ag via MHC class I molecules to CD8(+) T cells. DCs are specialized cross-presenting cells and as such have a critical role in antitumor immunity. DCs are routinely found within the tumor microenvironment, but their capacity for endogenous or therapeutically enhanced(More)
OBJECTIVES The immune effects of EGFR tyrosine kinase inhibitors (EGFR-TKIs) are poorly understood. Identifying immune biomarkers could guide patient selection and optimisation of EGFR-TKI-immunotherapy combinations. MATERIALS AND METHODS 33 patients with NSCLC treated with an EGFR-TKI were prospectively enrolled. Peripheral blood mononuclear cells were(More)
One of the critical questions in tumor immunology is how the host senses the presence of the many potential antigens that are present in each tumor. It was initially thought that the host remained ignorant of the presence of a tumor unless the tumor cells themselves metastasize to the lymph nodes, and thus engage directly with host T cells. In line with(More)
Cross-presentation, which defines how antigen-presenting cells (APCs) such as dendritic cells (DCs) process and present exogenous antigens to CD8C T cells via major histocompatibility complex (MHC) class I molecules, is pivotal in an effective antitumor immune response. Cross-presentation of intracellular tumor antigens by lymph node DCs (LNDCs) is very(More)