Manipulation of PD-1 signaling may restore the host T-cell response and thus may have therapeutic potential. PD-1 also may serve as a biomarker to monitor host immunity among patients with tuberculosis during therapy and vaccine studies.

Objectives-Laparoscopic partial nephrectomy requires advanced training in minimally invasive techniques in order to accomplish precise tumor resection and renal reconstruction while minimizing warm ischemia times. Complex renal tumors may preclude a minimally invasive approach to nephron sparing surgery in some patients. We describe our technique, illustrated with video, of robotic partial nephrectomy for challenging renal tumors, including hilar, endophytic, and multiple tumors.Methods-Robotic assistance was used to resect 14 tumors in eight patients (mean age 50.3 years, range 30-68 years). Three patients had hereditary kidney cancer. All patients had complex tumor features on preoperative imaging, including hilar tumors (five patients), endophytic tumors (four patients), and/or multiple tumors (three patients).Results-Robotic partial nephrectomy procedures were performed successfully without complications. Hilar clamping was utilized with a mean warm ischemia time of 31 minutes (range 24-45 minutes). Mean blood loss was 230 ml (range 100-450 ml). Histopathology confirmed clear cell renal cell carcinoma (n=3), hybrid oncocytic tumor (n=2), chromophobe renal cell carcinoma (n=2), and oncocytoma (n=1). All patients had negative surgical margins. Mean index tumor size was 3.6 cm (range 2.6-6.4 cm). Mean hospital stay was 2.6 days. At three months follow-up, no patients experienced perioperative complications or a statistically significant change in serum creatinine or estimated glomerular filtration rate and there was no evidence of tumor recurrence.Conclusions-Robotic partial nephrectomy is a safe and feasible approach for select patients with complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance may facilitate tumor resection and renal reconstruction for challenging cases, offering a minimally invasive surgical option for select patients with complex tumors who might otherwise require open surgery.

Our results highlight the importance of Treg cells in suppression of effector immune response and their influence on bacillary dissemination, disease manifestation, and severity.

BackgroundPrevious work from our laboratory has demonstrated that during acute viral brain infection, glial cells modulate antiviral T cell effector responses through the PD-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation. Here, we evaluated the PD-1: PD-L1 pathway in development of brain-resident memory T cells (bTRM) following murine cytomegalovirus (MCMV) infection.MethodsFlow cytometric analysis of immune cells was performed at 7, 14, and 30 days post-infection (dpi) to assess the shift of brain-infiltrating CD8+ T cell populations from short-lived effector cells (SLEC) to memory precursor effector cells (MPEC), as well as generation of bTRMs.ResultsIn wild-type (WT) animals, we observed a switch in the phenotype of brain-infiltrating CD8+ T cell populations from KLRG1+ CD127− (SLEC) to KLRG1− CD127+ (MPEC) during transition from acute through chronic phases of infection. At 14 and 30 dpi, the majority of CD8+ T cells expressed CD127, a marker of memory cells. In contrast, fewer CD8+ T cells expressed CD127 within brains of infected, PD-L1 knockout (KO) animals. Notably, in WT mice, a large population of CD8+ T cells was phenotyped as CD103+ CD69+, markers of bTRM, and differences were observed in the numbers of these cells when compared to PD-L1 KOs. Immunohistochemical studies revealed that brain-resident CD103+ bTRM cells were localized to the parenchyma. Higher frequencies of CXCR3 were also observed among WT animals in contrast to PD-L1 KOs.ConclusionsTaken together, our results indicate that bTRMs are present within the CNS following viral infection and the PD-1: PD-L1 pathway plays a role in the generation of this brain-resident population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0860-3) contains supplementary material, which is available to authorized users.

CD4+CD25+Foxp3+ Regulatory T cells (Treg) and programmed death-1 (PD-1) molecules have emerged as pivotal players in immune suppression of chronic diseases. However, their impact on the disease severity, therapeutic response and restoration of immune response in human tuberculosis remains unclear. Here, we describe the possible role of Treg cells, their M. tuberculosis driven expansion and contribution of PD-1 pathway to the suppressive function of Treg cells among pulmonary tuberculosis (PTB) patients. Multicolor flow cytometry, cell culture, cells sorting and ELISA were employed to execute the study. Our results showed significant increase in frequency of antigen-reactive Treg cells, which gradually declined during successful therapy and paralleled with decline of M. tuberculosis–specific IL-10 along with elevation of IFN-γ production, and raising the IFN-γ/IL-4 ratio. Interestingly, persistence of Treg cells tightly correlated with MDR tuberculosis. Also, we show that blocking PD-1/PD-L1 pathway abrogates Treg-mediated suppression, suggesting that the PD-1/PD-L1 pathway is required for Treg-mediated suppression of the antigen-specific T cells. Treg cells possibly play a role in dampening the effector immune response and abrogating PD-1 pathway on Treg cells significantly rescued protective T cell response, suggesting its importance in immune restoration among tuberculosis patients.

Suppression of T cell response is thought to be involved in the pathogenesis of visceral leishmaniasis (VL). Regulatory T cell (Treg) mediated immune-suppression is reported in animal models of Leishmania infection. However, their precise role among human patients still requires pathologic validation. The present study is aimed at understanding the frequency dynamics and function of Treg cells in the blood and bone marrow (BM) of VL patients. The study included 42 parasitologically confirmed patients, 17 healthy contact and 9 normal bone marrow specimens (NBM). We show i) the selective accumulation of Treg cells at one of the disease inflicted site(s), the BM, ii) their in vitro expansion in response to LD antigen and iii) persistence after successful chemotherapy. Results indicate that the Treg cells isolated from BM produces IL-10 and may inhibit T cell activation in IL-10 dependent manner. Moreover, we observed significantly higher levels of IL-10 among drug unresponsive patients, suggesting their critical role in suppression of immunity among VL patients. Our results suggest that IL-10 plays an important role in suppression of host immunity in human VL and possibly determines the efficacy of chemotherapy.

The 2-component tissue sealant provided immediate and durable hemostasis in laparoscopic partial nephrectomy. It is a safe and time sparing alternative adjunct to currently available means of achieving hemostasis. In a select patient population use of this agent may reduce warm ischemia time by circumventing the need to perform laparoscopic suturing.

Recent improvements in prostate cancer detection narrow the gap between the incidence and true prevalence of prostate cancer. This, however, raises concerns about the risk of over detection of latent cancers and thus identifying a need for improvement in screening strategies to better identify clinically significant disease.