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Course-based undergraduate research experiences (CUREs) have been shown to lead to multiple student benefits, but much is unknown about how CUREs lead to specific student outcomes. In this study, we examined the extent to which students making "broadly relevant novel discoveries" impacted student project ownership by comparing the experiences of students in a CURE and a traditional lab course. The CURE and traditional lab were similar in most aspects; students were exposed to an identical curriculum taught by the same instructor. However, there was one major difference between the two types of courses: the type of data that the students produced. Students in the traditional lab characterized the immune system of wild-type mice, thereby confirming results already known to the scientific community, while students in the CURE characterized the immune system of a mutant strain of mice, which produced broadly relevant novel discoveries. Compared with traditional lab students, CURE students reported higher cognitive and emotional ownership over their projects. Students' perceptions of collaboration and making broadly relevant novel discoveries were significantly and positively related to their cognitive and emotional ownership. This work provides insight into the importance of integrating opportunities for broadly relevant novel discoveries in lab courses.

The clinical use of adoptive immunotherapy with tumor-reactive T cells to treat established cancers is limited in part by the poor in vivo survival and function of the transferred T cells. Although administration of exogenous cytokines such as IL-2 can promote T cell survival, such strategies have many nonspecific activities and are often associated with toxicity. We show here that abrogating expression of Casitas B-lineage lymphoma b (Cbl-b), a negative regulator of lymphocyte activation, in tumor-reactive [CD8.sup.+] T cells expanded ex vivo increased the efficacy of adoptive immunotherapy of disseminated leukemia in mice. Mechanistically, Cbl-b abrogation bypassed the requirement for exogenous IL-2 administration for tumor eradication in vivo. In addition, [CD8.sup.+] T cells lacking Cbl-b demonstrated a lower threshold for activation, better survival following target recognition and stimulation, and enhanced proliferative responses as a result of both IL-2-dependent and -independent pathways. Importantly, siRNA knockdown of Cbl-b in human [CD8.sup.+][CD28.sup.-] effector T cell clones similarly restored IL-2 production and proliferation following target recognition independent of exogenous IL-2, enhanced IFN-γ production, and increased target avidity. Thus, abrogating Cbl-b expression in effector T cells may improve the efficacy of adoptive therapy of some human malignancies., Introduction Adoptive transfer of ex vivo expanded tumor-specific [CD8.sup.+] T cells has exhibited efficacy in the treatment of some malignant diseases (1-6). However, substantive obstacles to making T cell therapy [...]

Author(s): Yongliang Zhang [1, 5]; Joseph N. Blattman [1]; Norman J. Kennedy [2]; Julie Duong [1]; Thang Nguyen [1]; Ying Wang [1]; Roger J. Davis [2]; Philip D. Greenberg [1]; [...]

Interleukin (IL)-2 is currently used to enhance T-cell immunity but can have both positive and negative effects on T cells. To determine whether these opposing results are due to IL-2 acting differently on T cells depending on their stage of differentiation, we examined the effects of IL-2 therapy during the expansion, contraction and memory phases of the T-cell response in lymphocytic choriomeningitis virus (LCMV)-infected mice. IL-2 treatment during the expansion phase was detrimental to the survival of rapidly dividing effector T cells. In contrast, IL-2 therapy was highly beneficial during the death phase, resulting in increased proliferation and survival of virus-specific T cells. IL-2 treatment also increased proliferation of resting memory T cells in mice that controlled the infection. Virus-specific T cells in chronically infected mice also responded to IL-2 resulting in decreased viral burden. Thus, timing of IL-2 administration and differentiation status of the T cell are critical parameters in designing IL-2 therapies., Author(s): Joseph N. Blattman [1]; Jason M. Grayson [1]; E. John Wherry [1]; Susan M. Kaech [1]; Kendall A. Smith [2]; Rafi Ahmed (corresponding author) [1] Although originally defined as [...]