Background: Exosomes, via heat shock protein 70 (HSP70) expressed in their membrane, are able to interact with the toll-like receptor 2 (TLR2) on myeloid-derived suppressive cells (MDSCs), thereby activating them. Methods: We analyzed exosomes from mouse (C57Bl/6) and breast, lung, and ovarian cancer patient samples and cultured cancer cells with different approaches, including nanoparticle tracking analysis, biolayer interferometry, FACS, and electron microscopy. Data were analyzed with the Student’s t and Mann-Whitney tests. All statistical tests were two-sided. Results: We showed that the A8 peptide aptamer binds to the extracellular domain of membrane HSP70 and used the aptamer to capture HSP70 exosomes from cancer patient samples. The number of HSP70 exosomes was higher in cancer patients than in healthy donors (mean, ng/mL ± SD = 3.5±1.7 vs 0.17±0.11, respectively, P = .004). Accordingly, all cancer cell lines examined abundantly released HSP70 exosomes, whereas “normal” cells did not. HSP70 had higher affinity for A8 than for TLR2; thus, A8 blocked HSP70/TLR2 association and the ability of tumor-derived exosomes to activate MDSCs. Treatment of tumor-bearing C57Bl/6 mice with A8 induced a decrease in the number of MDSCs in the spleen and inhibited tumor progression (n = 6 mice per group). Chemotherapeutic agents such as cisplatin or 5FU increase the amount of HSP70 exosomes, favoring the activation of MDSCs and hampering the development of an antitumor immune response. In contrast, this MDSC activation was not observed if cisplatin or 5FU was combined with A8. As a result, the antitumor effect of the drugs was strongly potentiated. Conclusions: A8 might be useful for quantifying tumor-derived exosomes and for cancer therapy through MDSC inhibition.

Standard treatment of high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor is intravesical instillation with Bacillus Calmette-Guérin (BCG) (induction and maintenance regimens); however, BCG therapy still fails in 30%-40% of patients. Prior studies suggest that programmed death-ligand 1 (PD-L1) expression and alterations in immune infiltration might be associated with BCG failure. The ALBAN trial is an international, 1 : 1 randomized, open-label phase III trial comparing the combination of atezolizumab (an anti-PD-L1 antibody) and BCG (arm B) versus BCG alone (arm A) for BCG-naive patients with high-risk NMIBC. The primary endpoint was investigator-assessed event-free survival (EFS). Key secondary endpoints included high-grade recurrence-free survival, complete response rate, and duration of response in patients with carcinoma in situ disease, as well as overall survival. In total, 255 patients were randomly assigned to arm A and 262 to arm B. The trial did not meet its primary endpoint; there was no significant difference in EFS between arms, with a hazard ratio of 0.98 (95% confidence interval 0.71-1.36, P = 0.9106). EFS results were consistent across all prespecified subgroups. The safety profile of the treatment combination was consistent with that of the individual agents but showed higher rates of treatment-related adverse events (TRAEs) and grade ≥3 TRAEs than BCG alone. This phase III trial in BCG-naive patients with high-risk NMIBC did not demonstrate an EFS benefit from the addition of atezolizumab to 1-year BCG therapy, in contrast to positive EFS results reported with another PD-(L)1 agent, suggesting that any benefit from checkpoint-BCG therapy may be context- and agent-specific rather than a class effect. Future research should focus on biomarker-driven patient selection and optimization of the timing, duration, and route of checkpoint delivery relative to BCG.

Background: Angiomyolipoma (AML) is the most common renal benign tumor. Treatment should be considered for symptomatic patients or for those at risk for complications, especially retroperitoneal bleeding which is correlated to tumor size, grade of the angiogenic component and to the presence of tuberous sclerosis complex (TSC). This study reports our single-center experience with the use of selective arterial embolization (SAE) in the management of symptomatic and asymptomatic renal AMLs. Methods: In this retrospective mono-centric study, all demographic and imaging data, medical records, angiographic features, outpatient charts and follow-up visits of patients who underwent prophylactic or emergency SAE for AMLs between January 2005 and July 2016 were reviewed. Tumor size and treatment outcomes were assessed at baseline and after the procedure during follow-up. Computed tomography (CT), magnetic resonance imaging (MRI) or ultrasonography was used to evaluate AML shrinkage. Renal function was measured pre- and post-procedure. Results: Twenty-three patients (18 females, 5 males; median age, 45 years; range, 19–85 years) who underwent SAE either to treat bleeding AML (n=6) or as a prophylactic treatment (n=17) were included. Overall, 34 AMLs were embolized. TSC status was confirmed for 6 patients. Immediate technical success rate was 96% and 4 patients benefitted from an additional procedure. Major complications occurred in 3 patients and minor post-embolization syndrome (PES) in 14 patients. The mean AML size reduction rate was 26.2% after a mean follow-up was 20.5 months (range, 0.5–56 months), and only non-TSC status was significantly associated with better shrinkage of tumor (P=0.022). Intralesional aneurysms were significantly more frequent in patients with hemorrhagic presentation (P=0.008). There was no change in mean creatinine level after SAE. Conclusions: SAE is a safe and effective technique to manage renal AMLs as a preventive treatment as well as in emergency setting, with significant reduction in tumor size during follow-up. A multidisciplinary approach remains fundamental, especially for TSC patients. In addition to size, the presence of intralesional aneurysms should be considered in any prophylactic treatment decision.

Blood baseline neutrophil count predicts bevacizumab efficacy in glioblastoma