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Abstract B38: Non-cytotoxic effects of the chemotherapeutic agent gemcitabine can alter the immunophenotype of tumor cells in in vitro culture
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In addition to their cytotoxic/cytostatic properties, some chemotherapeutics have shown a remarkable capacity to modulate immune response. One such chemotherapy is the antimetabolite, gemcitabine (GEM). GEM has been shown to influence the quantity and activation of certain immune cell subsets when used in vivo. It has also been demonstrated that administration of GEM in conjunction with immunotherapy, such as dendritic cell vaccination, is beneficial in terms of overall survival and progression-free survival. The purpose of this study is to investigate if GEM can influence the way that tumor cells surviving treatment are regarded by the immune system. Our group has found that short-term in vitro culture with GEM enhances expression of human leukocyte antigen (HLA) class I, CD95, NKG2D ligands and TRAIL receptors on tumor cell lines. These molecules are all cell surface proteins important for the efficient surveillance and effector function of the immune system. The HLA class I increase is beta-2-microglobulin dependent and changes are underpinned by ERK, JNK and RelB-NFkB signalling pathways. Furthermore, culture with GEM induces immunoproteasomal components LMP2 and MECL-1 in tumor cells and, subsequently, the peptide antigen repertoire displayed on HLA class I is altered. The changes in peptide characteristics include amino acid anchor residue modifications which render the peptides likely to favor binding alternative HLA-allotypes. The renovation of the peptidome displayed by HLA class I may reveal sub-dominant immunogens to T-cells. Taken together, these changes may render tumor cells more sensitive to immune cell-mediated lysis. These data help explain observations made in previous in vivo studies, advise as to which novel antigens could be utilised in future vaccination protocols and lend further credence to the idea that chemotherapy and immunotherapy could be used in combination.
Citation Format: Andrew M. Gravett, John P. Copier, Wai M. Liu, Martin P. Cranage, Angus G. Dalgleish. Non-cytotoxic effects of the chemotherapeutic agent gemcitabine can alter the immunophenotype of tumor cells in in vitro culture. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B38.</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Modulation of the adaptive immune system through chronic inflammation and T-regulatory responses
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