Sally Fischer

Various cytokines have been evaluated as potential anticancer drugs; however, most cytokine trials have shown relatively low efficacy. Here, we found that treatments with IL-12 and IL-18 or with a mutant form of IL-2 provided substantial therapeutic benefit for mice specifically bearing MHC class I-deficient tumors, but these treatments were ineffective for mice with matched MHC class I+ tumors. Cytokine efficacy was linked to the reversal of the anergic state of NK cells that specifically occurred in MHC class I-deficient tumors, but not MHC class I+ tumors. NK cell anergy was accompanied by impaired early signal transduction and was locally imparted by the presence of MHC class I-deficient tumor cells, even when such cells were a minor population in a tumor mixture. These results demonstrate that MHC class I-deficient tumor cells can escape from the immune response by functionally inactivating NK cells, and suggest cytokine-based immunotherapy as a potential strategy for MHC class I-deficient tumors. These results suggest that such cytokine therapies would be optimized by stratification of patients. Moreover, our results suggest that such treatments may be highly beneficial in the context of therapies to enhance NK cell functions in cancer patients.

In my dissertation I present Merleau-Ponty's conception of embodied inter-subjectivity as a fruitful starting point from which to formulate an ethics. While Merleau-Ponty himself never wrote an ethics, my own analysis aims to draw out the ethical dimension already implied in his epistemological, and later ontological understanding of embodied inter-subjectivity. Since Merleau-Ponty rejects the sovereign, individualistic subject of Modernity in favor of a dialogical subject embedded in language and in history, we will not find a systematic ethics. Rather, an ethics elicited from Merleau-Ponty's philosophy will center around the mode of interpersonal relations. I make a case for a kind of ethics that includes a call for a general shift in the way we understand ourselves and live our lives with others, rather than a call for an ahistorical set of maxims. An ethical shift can mean a shift in discursive structures and a shift from a mode of "having" to a mode of "being" , where being is dialogical and the other is not reduced to utility but is a genuine interlocutor in the dialogue. Merleau-Ponty's account of language and history make possible a shift to be incorporated into an altered discursive framework, which in turn becomes incorporated into our daily lives. ;Central to my project, however, is also the articulation of those aspects of embodied subjectivity and of alterity that are problematic to providing a fecund ground for the ethical relation. In my argument I incorporate several feminist criticisms, including those of Judith Butler, Iris Young, and Luce Irigaray. On the one hand, I defend Merleau-Ponty's thought against claims that his philosophy of embodied subjectivity is inherently gender-biased and that his notion of alterity precludes genuine "otherness." On the other hand, I show that a reformulation of certain aspects of his understanding of embodied subjectivity is necessary in order to develop an ethics grounded in a hermeneutical, dialogical relation which remains open to difference. ;I argue that the necessary ingredient that makes possible an ethical responsibility to the other is an ethical recognition, a mode of being with another based on an obligation to maintain a kind of "availability" in which we remain open to calls placed on us by others. Ethical recognition in a Merleau-Pontyan sense is an obligation to keep the communicative process alive, maintaining a goal of genuine reciprocity. The communicative process is our capacity of reflection, expression, and gathering together the separate elements into a whole that does not subsume all the "parts" . Ethical relations hinge on what Merleau-Ponty calls a "presumptive" universality, which involves a continuous communicative process embodied in concrete dialogical practices. If we can speak of a utopia at all, we must recognize that utopia is not a static goal. A Merleau-Pontyan ethics, then, is a process of dialogue which aims at co-creating a common ground in a movement of continuously reworking itself through new perspectives