Frailty Testing Pilot Study: Pros and Pitfalls

Background: Frailty can be defined as an inflammatory state with a loss of physiologic reserve in multiple systems that manifests as a decreased ability to respond to stressors that ultimately leads to an increased risk of adverse outcomes. The aim of this study was to determine the ease of frailty testing in a pre-kidney transplant clinic and the resources required to do so. A secondary goal was to better understand the utility of frailty testing when evaluating potential kidney transplant recipients. Methods: Frailty testing was conducted at a pre-kidney transplant clinic in three phases using Fried\u27s frailty phenotype (shrinking, exhaustion, low physical activity, slowness, and grip strength). Results: A total of 132 frailty tests were completed on 128 patients. Frail patients had significantly higher rates of shrinking (26% vs. 8.5%, P \u3c 0.05), exhaustion (82.6% vs. 27.6%, P \u3c 0.05), low physical activity (78.2% vs. 19.0%, P \u3c 0.05), slow walking (60.8% vs. 15.2%, P \u3c 0.05), and grip strength (73.9% vs. 25.7%, P \u3c 0.05). When comparing the listing of frail and non-frail patients for transplant, a significantly lower proportion of frail patients were listed compared to non-frail patients (30.4% vs. 57.6%, P \u3c 0.05). Frailty testing was most complete when an examiner dedicated to frailty testing performed the testing. Conclusions: Frailty testing is feasible to complete in a pre-transplant clinic with an appropriate investment in personnel and resources

Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells

Transplanted donor lymphocytes infused during hematopoietic stem cell transplantation (HSCT) have been shown to cure patients with hematological malignancies. However, less is known about the effects of HSCT on metastatic solid tumors. Thus, a better understanding of the immune cells and their target antigens that mediate tumor regression is urgently needed to develop more effective HSCT approaches for solid tumors. Here we report regression of metastatic renal cell carcinoma (RCC) in patients following nonmyeloablative HSCT consistent with a graft-versus-tumor effect. We detected RCC-reactive donor-derived CD8+ T cells in the blood of patients following nonmyeloablative HSCT. Using cDNA expression cloning, we identified a 10-mer peptide (CT-RCC-1) as a target antigen of RCC-specific CD8+ T cells. The genes encoding this antigen were found to be derived from human endogenous retrovirus (HERV) type E and were expressed in RCC cell lines and fresh RCC tissue but not in normal kidney or other tissues. We believe this to be the first solid tumor antigen identified using allogeneic T cells from a patient undergoing HSCT. These data suggest that HERV-E is activated in RCC and that it encodes an overexpressed immunogenic antigen, therefore providing a potential target for cellular immunity