IntroductionAvascular necrosis of femoral head (ANFH) is a progressive disease that often leads to hip joint dysfunction and even disability in young patients. Although the standard treatment, which is core decompression, has the advantage of minimal invasion, the efficacy is variable. Recent studies have shown that implantation of bone marrow containing osteogenic precursors into necrotic lesion of ANFH may be promising for the treatment of ANFH.MethodsA prospective, double-blinded, randomized controlled trial was conducted to examine the effect of bone-marrow buffy coat (BBC) grafting combined with core decompression for the treatment of ANFH. Forty-five patients (53 hips) with Ficat stage I to III ANFH were recruited. The hips were allocated to the control group (core decompression + autologous bone graft) or treatment group (core decompression + autologous bone graft with BBC). Both patients and assessors were blinded to the treatment options. The clinical symptoms and disease progression were assessed as the primary and secondary outcomes.ResultsAt the final follow-up (24 months), there was a significant relief in pain (P <0.05) and clinical joint symptoms as measured by the Lequesne index (P <0.05) and Western Ontario and McMaster Universities Arthritis Index (P <0.05) in the treatment group. In addition, 33.3% of the hips in the control group have deteriorated to the next stage after 24 months post-procedure, whereas only 8% in the treatment group had further deterioration (P <0.05). More importantly, the non-progression rates for stage I/II hips were 100% in the treatment group and 66.7% in the control group.ConclusionImplantation of the autologous BBC grafting combined with core decompression is effective to prevent further progression for the early stages of ANFH.Trial registrationClinicalTrials.gov identifier NCT01613612. Registered 13 December 2011.

Although dendritic cell (DC) dysfunction in cancer is a well-recognized consequence of cancer-associated inflammation that contributes to immune evasion, the mechanisms that drive this process remain elusive. Here, we show the critical importance of tumor-derived TLR2 ligands in the generation of immunosuppressive IL-10-producing human and mouse DCs. TLR2 ligation induced two parallel synergistic processes that converged to activate STAT3: stimulation of autocrine IL-6 and IL-10 and upregulation of their respective cell surface receptors, which lowered the STAT3 activation threshold. We identified versican as a soluble tumor-derived factor that activates TLR2 in DCs. TLR2 blockade in vivo improved intra-tumor DC immunogenicity and enhanced the efficacy of immunotherapy. Our findings provide a basis for understanding the molecular mechanisms of DC dysfunction in cancer and identify TLR2 as a relevant therapeutic target to improve cancer immunotherapy.