Dendritic cell maturation in active immunotherapy strategies

Dendritic cells (DCs) loaded with tumour antigen have become the centrepiece of clinical trials testing active immunotherapy strategies. Important variables include the source of DCs, the choice of antigens, the method of antigen loading and the route and timing of administration. Recently, the requirement for and the method of, DC maturation have been receiving particular attention. This is due to observations from in vitro studies and animal models demonstrating that mature DCs induce more potent antigen-specific T-cells responses than immature DCs. Furthermore, preliminary observations in human studies suggest that immature DCs might actually downregulate antigen-specific T-cell responses but mature DCs may augment them. Current studies are addressing how to define DC maturation, whether the variety of methods for maturation result in DCs with similar T-cell stimulatory capacity, how to maintain the maturational status and whether maturation in vitro before immunisation, or in vivo, after immunisation, results in better DC function.     

Immunotherapy for renal cell carcinoma

Introduction: Advanced renal cell cancers (aRCC) has historically been responsive to immune system manipulation. A better understanding of the anti-tumor immune response has fueled the emergence of immunotherapy-based regimens, including combinations with vascular endothelial growth factor (VEGF) inhibitors.

Areas covered: In this review, we will describe the historic use of immunotherapies and their integration with newer agents, specifically in clear cell aRCC.

Expert opinion: Novel immunotherapeutic agents, as well as combinations with VEGF/TKI therapy, will become the standard of care initial therapy in the management of aRCC. Further studies in the sequencing of drug administration, managing treatment-related adverse events (TRAE), and exploring innovative approaches are warranted.     

Clear cell renal cell carcinoma

Clear cell RCC is the most common type of RCC that occurs in adults. It has the worst prognosis among the common epithelial tumors of the kidney. Histologically, a wide range of morphologic patterns can be encountered. Those cases with a multi-locular cystic architecture are considered to be a distinct subtype because of the clinicopathologic features.     

腹腔镜肾癌根治术

目的 报道腹腔镜肾癌根治性切除术的经验。方法 2001年11月一2002年12月共收治肾癌13例，男性8例，女性5例，年龄36—78岁(平均57岁)。左侧6例，右侧7例，11例肿瘤直径小于5cm，采用后腹腔镜肾癌根治术。2例肿瘤直径分别为7．8及8．9cm，采用手辅式腹腔镜肾癌根治术。结果 12例腹腔镜肾癌根治手术成功，1例左肾动脉损伤改开放手术。手术时间67—213min，平均162min。术中出血量约80。400ml之间，平均120ml。8例穿刺口周围不同程度皮下气肿，3d后自行消失。术后24h下床活动，48h开始进食，术后7d出院。随访1—1．5年，13例无肿瘤复发，无穿刺孔种植转移。结论 腹腔镜肾癌根治术是一种安全，有效的治疗方法。     

Antigenic targets for renal cell carcinoma immunotherapy

Renal cell carcinoma (RCC) has been shown to respond to immunotherapeutic intervention, thus fostering continued interest in exploiting the ability of the immune system to recognise and eradicate renal malignancy. Considerable progress in the characterisation of tumour-associated antigens, coupled with the appreciation that dendritic cells act as master regulators of immunity and tolerance, has opened new possibilities for immunotherapeutic intervention against human cancer. However, in contrast to other tumour systems, clinically relevant antigens expressed by RCC have not yet been identified. Therefore, most RCC vaccine trials have employed unfractionated antigens derived from tumour cells, with the goal of eliciting T cell responses against many unknown antigens expressed by the tumour. The recent discovery of genes with critical roles in oncogenesis has facilitated the identification of novel, more universal targets that may make cancer vaccines more practical, applicable and, potentially, more effective. In addition, immunisation against tumour antigens can be combined with tumour stroma-associated targets, thereby exerting a synergistic antitumour effect. Continued identification of molecular targets, in concert with more effective vaccination protocols, is likely to produce vaccination strategies with clinical impact.     

Bilateral renal cell carcinoma

Renal carcinoma is frequently detected incidentally during abdominal ultrasound studies or computed tomographic scanning. Although clinical studies report bilateral tumors in fewer than 4 percent of patients with renal carcinoma, an autopsy study has shown a much higher incidence. Various surgical approaches are available.     

Antigenic targets for renal cell carcinoma immunotherapy

Renal cell carcinoma (RCC) has been shown to respond to immunotherapeutic intervention, thus fostering continued interest in exploiting the ability of the immune system to recognise and eradicate renal malignancy. Considerable progress in the characterisation of tumour-associated antigens, coupled with the appreciation that dendritic cells act as master regulators of immunity and tolerance, has opened new possibilities for immunotherapeutic intervention against human cancer. However, in contrast to other tumour systems, clinically relevant antigens expressed by RCC have not yet been identified. Therefore, most RCC vaccine trials have employed unfractionated antigens derived from tumour cells, with the goal of eliciting T cell responses against many unknown antigens expressed by the tumour. The recent discovery of genes with critical roles in oncogenesis has facilitated the identification of novel, more universal targets that may make cancer vaccines more practical, applicable and, potentially, more effective. In addition, immunisation against tumour antigens can be combined with tumour stroma-associated targets, thereby exerting a synergistic antitumour effect. Continued identification of molecular targets, in concert with more effective vaccination protocols, is likely to produce vaccination strategies with clinical impact.     

Radiogenomics in renal cell carcinoma

Abdominal Radiology - Radiogenomics, a field of radiology investigating the association between the imaging features of a disease and its gene expression pattern, has expanded considerably in the...     

Inhibition of lung metastases of murine renal cell carcinoma by the combination of radiation and interferon-alpha-producing tumor cell vaccine

We have previously demonstrated in a murine lung metastasis model that local sublethal radiation of tumors can synergistically enhance their sensitivity to immunotherapy with either systemic high-dose interleukin-2 (IL-2) or vaccination with autologous tumor cells expressing IL-2, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF). Host antitumor activity was mediated in large part by natural killer cells, which can be activated by IFN-alpha. In the present study, we used this lung metastasis model to investigate the efficacy of combined therapy with local tumor radiation and vaccination with IFN-alpha-secreting tumor cells (Renca/IFN-alpha). The in vitro and in vivo growth rates of Renca/IFN-alpha cells were significantly reduced relative to normal controls. Subcutaneous vaccination with Renca/IFN-alpha or selective X-irradiation of the left lung (300 rad) reduced the number of lung tumors by 40% and 27%, respectively. The combination of lung irradiation plus vaccination reduced the number of lung metastases by 60%, and the net tumor volume by 95%. The reductions in tumor volume in both irradiated and non-irradiated lungs were comparable. These results indicate that host antitumor response to subcutaneous vaccination with Renca/IFN-alpha was systemic, and was significantly enhanced by radiation of tumor-bearing lungs. A regimen based on enhancement of IFN-alpha immunotherapy by local tumor radiation may be useful in the treatment of metastatic renal cell carcinoma.     

能谱CT鉴别肾脏嗜酸性细胞腺瘤和嫌色细胞癌

目的观察能谱CT多参数鉴别诊断肾脏嗜酸细胞腺瘤(RO)与嫌色细胞型肾癌(CRCC)的价值。方法回顾性分析经手术病理证实的12例RO(RO组)和30例CRCC(CRCC组)患者,测量并计算皮/髓质期70 keV单能量CT值、碘浓度(IC)、标准化碘浓度(NIC)、水浓度(WC)、有效原子序数及40～70 keV能谱曲线斜率(λ值)。比较2组常规CT征象及能谱CT参数差异,以ROC曲线评估差异有统计学意义的参数鉴别RO与CRCC的效能。结果 2组常规CT显示病灶中心瘢痕出现率差异有统计学意义(χ²=3.038,P=0.046)。能谱CT参数中,RO组皮/髓质期70 KeV单能量CT值、IC、有效原子序数、λ值及皮质期NIC均高于CRCC组(P均<0.05),髓质期NIC及皮/髓质期WC与CRCC组差异均无统计学意义(P均>0.05)。以皮质期λ值5.68为阈值鉴别RO与CRCC的AUC最高为1.00(P<0.01),敏感度及特异度均为100%。结论能谱CT参数,包括皮/髓质期70 keV单能量CT值、IC、有效原子序数、λ值及皮质期NIC对鉴别RO与...