Targeting TBK1 to overcome resistance to cancer immunotherapy

Despite the success of PD-1 blockade in melanoma and other cancers, effective treatment strategies to overcome resistance to cancer immunotherapy are lacking1,2. Here we identify the innate immune kinase TANK-binding kinase 1 (TBK1)3 as a candidate immune-evasion gene in a pooled genetic screen4. Using a suite of genetic and pharmacological tools across multiple experimental model systems, we confirm a role for TBK1 as an immune-evasion gene. Targeting TBK1 enhances responses to PD-1 blockade by decreasing the cytotoxicity threshold to effector cytokines (TNF and IFNγ). TBK1 inhibition in combination with PD-1 blockade also demonstrated efficacy using patient-derived tumour models, with concordant findings in matched patient-derived organotypic tumour spheroids and matched patient-derived organoids. Tumour cells lacking TBK1 are primed to undergo RIPK- and caspase-dependent cell death in response to TNF and IFNγ in a JAK-STAT-dependent manner. Taken together, our results demonstrate that targeting TBK1 is an effective strategy to overcome resistance to cancer immunotherapy

Examination of the Psychometric Properties of the Personal Growth Initiative Scale-II in African American College Students

Personal growth initiative (PGI), an individual\u27s active and intentional desire to engage in the growth process, has been an important construct in studies of physical and mental health around the world. However, there is a dearth of research examining this construct in African American samples. In addition, PGI has recently undergone a revision of both its theory and measure; the resulting Personal Growth Initiative Scale-II (PGIS-II) has been validated for use only with European American and international college student samples. The current study examined the psychometric properties of the PGIS-II in a sample of African American college students. Confirmatory factor analyses yielded results consistent with previous studies, and the PGIS-II showed evidence of convergent and discriminant validity for three of its four factors. In addition, the PGIS-II was significantly related to aspects of Black racial identity, suggesting that it is a viable construct in this population