PD-L1+ regulatory B cells act as a T cell suppressor in a PD-L1-dependent manner in melanoma patients with bone metastasis.
在黑色素瘤pa t ien t s wi T h骨me t中，PD-L1 + 调节t t细胞ac t以PD-L1-dependen t方式作为t细胞抑制因子。
- 作者列表："Wu H","Xia L","Jia D","Zou H","Jin G","Qian W","Xu H","Li T
:The five-year survival rate of melanoma worsens significantly with advancing tumor stage. We hypothesized that regulatory B cells (Breg) might have participated in the pathogenesis of melanoma. In this study, the PD-L1+ Breg cells were investigated. The expression of PD-L1 by circulating B cells was very low in healthy controls. In melanoma patients, on the other hand, the expression of PD-L1 by circulating B cells was significantly elevated in a manner that was positively associated with tumor stage, with the highest level in stage IV bone metastasis patients. Compared to total B cells, PD-L1+ B cells presented higher IgM and higher IgD expression, and were almost exclusively CD20+CD27-, suggesting that the PD-L1+ B cells exhibited a naive B cell-like phenotype. Healthy naive B cells, which presented little PD-L1, and stage I and stage II melanoma patient naive B cells, which presented detectable but low PD-L1, were unable to suppress T cell response. However, stage III and stage IV naive B cells, which presented moderate PD-L1, could significantly suppress T cell response in a PD-L1-dependent manner. We further found that the level of PD-L1+ B cells was significantly higher in bone metastasis than in the primary tumors. Overall, we demonstrated that PD-L1+ B cells were upregulated in advanced melanoma and were enriched in metastasis compared to primary tumors. Furthermore, PD-L1+ naive B cells could act as a T cell suppressor in a PD-L1-dependent manner.
: 随着肿瘤分期的进展，黑色素瘤的五年生存率显著恶化。我们假设调节性B细胞 (Breg) 可能参与了黑色素瘤的发病机制。在这项研究中，PD-L1 + Breg细胞进行了调查。健康对照组循环b细胞PD-L1 的表达很低。另一方面，在黑色素瘤患者中，循环b细胞PD-L1 的表达显著升高，与肿瘤分期呈正相关。以 ⅳ 期骨转移患者水平最高。与总b细胞相比，PD-L1 + b细胞表现出较高的IgM和较高的IgD表达，并且几乎完全是CD20 + CD27-，提示PD-L1 + b细胞呈现幼稚b细胞样表型。健康的幼稚b细胞，呈现很少的PD-L1，I期和II期黑色素瘤患者幼稚b细胞，呈现可检测但低PD-L1，无法抑制T细胞应答。然而，III期和IV期幼稚b细胞，呈现中度PD-L1，可以以PD-L1-dependent的方式显著抑制T细胞应答。我们进一步发现PD-L1 + b细胞水平在骨转移中明显高于原发肿瘤。总体而言，我们证明PD-L1 + b细胞在晚期黑色素瘤中上调，并且与原发性肿瘤相比在转移中富集。此外，PD-L1 + 幼稚b细胞可以以PD-L1-dependent的方式作为T细胞抑制因子。
METHODS:OBJECTIVE:Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS: :Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS: :Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION:Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE: :This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.
METHODS:BACKGROUND:National guidelines recommend screening and treatment for cancer-related bone disease and continued monitoring of bone-modifying agents. It is unclear whether a standardized screening tool is utilized to identify eligible patients and ensure appropriate supportive care is implemented. The purpose of this study was to evaluate current prescribing practices and optimize management of bone-modifying agents. METHODS:A retrospective chart review was performed to identify patients who received hormone deprivation therapy or had bone metastases through Hematology/Oncology or Urology clinics from 1 November 2016 to 31 October 2017. The primary endpoints of this study were the incidence of completed baseline dual-energy X-ray absorptiometry (DEXA) scan for patients on hormone deprivation therapy and percent of patients started on a bone-modifying agent for the prevention of skeletal-related events secondary to bone metastasis. Secondary endpoints included percent of patients with dental examinations prior to initiation, adequate calcium and vitamin D supplementation, incidence of osteonecrosis of the jaw or flu-like symptoms and education, and percent of bisphosphonate doses appropriately adjusted based on renal function. RESULTS:A total of 375 patients were assessed for baseline DEXA scans and bone-modifying therapy. Of the 226 patients on hormone deprivation therapy, 111 (49%) patients were appropriately screened with a DEXA scan prior to initiation of hormone deprivation therapy. Among the 149 patients with bone metastases, only 94 (63.1%) patients were started on a bone-modifying agent. CONCLUSIONS:Opportunities have been identified to optimize management of patients with cancer-related bone disease. Implementation of standardized tools may increase the rate of appropriate screening and initiation of bone-modifying therapy when warranted.
METHODS:PURPOSE:Low skeletal muscle mass has been associated with poor prognosis in patients with advanced lung cancer. However, little is known about the relationship between skeletal muscle mass and overall survival in patients with bone metastases from lung cancer. The objective of the present study was to evaluate the prognostic value of low trunk muscle mass in predicting overall survival in these patients. METHODS:The data from 198 patients who were diagnosed with bone metastases from lung cancer from April 2009 to May 2017 were retrospectively reviewed. The areas of the psoas and paravertebral muscles were measured at the level of the third lumbar vertebra on computed tomography scans taken at the time nearest to the diagnosis of bone metastasis. Muscle area was evaluated for male and female cohorts separately using different cutoff points. Cox proportional hazards analysis was performed to evaluate the factors independently associated with overall survival. RESULTS:The overall survival of patients in the lowest quartile for psoas muscle area or paravertebral muscle area was significantly shorter than that of patients above the 25th percentile for muscle area (p < 0.001). Multivariate analyses showed that paravertebral muscle mass (hazard ratio, 1.73; 95% confidence interval, 1.17-2.56; p = 0.006), epidermal growth factor receptor-targeted therapy, and performance status were independent prognostic factors. CONCLUSIONS:Low paravertebral muscle mass was associated with shorter survival, independently of known prognostic factors.