Expression of Programmed Cell Death Ligand 1 and Associated Lymphocyte Infiltration in Olfactory Neuroblastoma.
嗅神经母细胞瘤中程序性细胞死亡配体 1 的表达及相关淋巴细胞浸润。
- 作者列表："London NR Jr","Rooper LM","Bishop JA","Xu H","Bernhardt LJ","Ishii M","Hann CL","Taube JM","Izumchenko E","Gaykalova DA","Gallia GL
BACKGROUND:Programmed cell death ligand 1 (PD-L1) is a transmembrane glycoprotein that interacts with the receptor programmed cell death 1 (PD-1) to suppress T-cell activation, reduce adjacent tissue damage, and promote tolerance to self-antigens. Tumors may express PD-L1 as a mechanism to evade immune detection. Recent clinical trials have demonstrated the efficacy of PD-L1/PD-1 antagonists through activation of tumor-infiltrated CD8+ T cells. The aim of this study was to determine the expression pattern of PD-L1 and PD-1 in olfactory neuroblastoma (ONB) tumor cells and to determine the presence of PD-1+ and CD8+ lymphocytes in the ONB immune microenvironment. METHODS:Immunohistochemistry for expression of PD-L1, PD-1, and CD8 was performed on paraffin-embedded ONB tissue. RESULTS:Of the 10 primary site ONB samples, 4 demonstrated positive PD-L1 expression. Of PD-L1+ tumors, the 2 highest expressing samples were found to contain PD-1+ tumor cells. Of the 4 available metastatic samples, all of which arose from PD-L1- primary site ONB, 3 were positive for PD-L1 and contained PD-1+ tumor cells. PD-L1+ primary and metastatic tumors also demonstrated increased PD-1+ infiltrating lymphocytes in the tumor and stroma (11.6- and 4.62-fold increase) compared with PD-L1- samples (P < 0.05 and P = 0.068 respectively). PD-L1+ specimens demonstrated increased CD8+ lymphocytes in the tumor and stroma (7.46- and 2.14-fold increase) compared with PD-L1- tumors (P < 0.05 for both). CONCLUSIONS:These data demonstrate that a proportion of ONB primary and metastatic tumors express PD-L1 and possess an associated tumor and stromal infiltrate of PD-1+ and CD8+ lymphocytes.
背景: 程序性细胞死亡配体 1 (PD-L1) 是一种跨膜糖蛋白，与受体程序性细胞死亡受体 1 (PD-1) 相互作用，抑制T细胞活化，减少邻近组织损伤，并促进对自身抗原的耐受性。肿瘤可能表达PD-L1 作为逃避免疫检测的机制。最近的临床试验已经证明了PD-L1/PD-1 拮抗剂通过激活肿瘤浸润的CD8 + T细胞的功效。本研究的目的是确定嗅神经母细胞瘤 (ONB) 中PD-L1 和PD-1 的表达模式。肿瘤细胞和确定ONB免疫微环境中是否存在PD-1 + 和CD8 + 淋巴细胞。 方法: 采用免疫组织化学方法检测石蜡包埋组织中PD-L1 、PD-1 和CD8 的表达。 结果: 10 例原发部位ONB标本中，4 例呈阳性PD-L1 表达。在PD-L1 + 肿瘤中，发现 2 个最高表达的样本含有PD-1 + 肿瘤细胞。在 4 个可用的转移样本中，全部来自PD-L1 原发部位ONB，3 个PD-L1 阳性，含有PD-1 + 肿瘤细胞。PD-L1 + 原发和转移性肿瘤也显示肿瘤和间质中PD-1 + 浸润淋巴细胞增加 (增加 11.6 倍和 4.62 倍) 与PD-L1 样本相比 (P < 0.05 和P = 0.068)。PD-L1 + 标本显示肿瘤和间质中CD8 + 淋巴细胞增加 (分别是PD-L1 肿瘤的 7.46 倍和 2.14 倍) (P均 <0.05)。 结论: 这些数据表明，部分ONB原发性和转移性肿瘤表达PD-L1，并具有相关肿瘤和PD-1 + 和CD8 + 淋巴细胞间质浸润。
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.