Objective:To select an appropriate dosage of IL-2 for tumor infiltrating lymphocyte(TIL).Methods:Isolated by the attachment method we established,TIL was cultivated in self-supernatant of malignant pleura,with three different concentrations of IL-2,such as 6000u per ml,6000u per ml for the first administration followed by 1000u per ml,or 1000u per ml.The expansion,killing activity and phenotype changes of TIL cultured in different cultures were assessed.Results:As cultured in self-supernatant of malignant pleura fluid,the concentrations of IL-2,such as 6000u per ml or 6000u per ml for the first administration followed by 1000u per ml seemed benefit for TIL proliferation.Conclusion:6000u per ml of IL-2 for the first administration was very important.It could help TIL to activate and proliferate early.The study described here offers the possibility for TIL cultured in vitro self-supernatant of malignant pleura fluid in vitro for a short time,and then reinfuse to thorax for further expanding and controlling the malignant pleura effusion in the presence of IL-2,and thereby minimizing the risks of contamination.

Chemoimmunotherapy or biochemotherapy, the combination of chemotherapy with immunotherapy, is a novel compre-hensive treatment model for malignant carcinoma. In recent years, many clinical trials have shown that biochemotherapy is associated with an improved response rate. Such biological agents include tumor vaccines, monoclonal antibodies, cytokines, and immunocompe-tent cells. In this article, we review the theories, sort the clinical applications of novel treatments, and discuss some of the problems existing in this field.

Objective:To study the effect of autologous supernatant of malignant pleura effusion and RPMI1640 with 10% AB+ serum on the culture of tumor infiltrating lymphocytes (TIL) in vitro. Methods:Isolated by the attachment method we established, TIL was cultured in either autologous supernatant of malignant pleura fluid or RPMI1640 with 10% AB+ serum, and various types of cytokines such as (IL-2,) PHA and antibody against CD3 (OKT3) were added into both cultures. The proliferation as well as the killing activity and the phenotype changes of TIL cultured in the two kinds of cultures were compared. Results:There was no difference in the proliferation or the killing activity in vitro as well as the phenotype changes of TIL between the two kinds of cultures. Conclusion: Autologous supernatant of malignant pleura fluid could be used as TIL culture medium. The method described here made it possible for TIL to be cultured in vitro for a short time, and then reinfused back to thorax for further expanding and controlling the malignant pleura effusion in the presence of IL-2, and it alsominimized the risks of contamination.

Objective:The aim of this study was to investigate the association of mRNA expressions of ERCC1 (excision repair cross-complementing group 1) and BRCA1 (breast cancer 1) with chemosensitivity to cisplatin in malignant pleural and peritoneal effusions.Methods:Malignant pleural and peritoneal effusions were collected from 46 patients diagnosed with stage Ⅳ malignant tumor, prospectively. The tumor cells were isolated and the sensitivity of tumor cells to cisplatin was detected by adenosine triphosphate-bioluminescence assay (ATP-TCA). Real-time quantitative PCR was used to determine the mRNA expressions of ERCC1 and BRCA1. Results:The expression level of ERCC1 mRNA was negatively correlated with sensitivity of non-small cell lung cancer (NSCLC) to cisplatin (P= 0.001, r=0.685). BRCA1 mRNA expression level had negative correlation with sensitivity to cisplatin in both NSCLC (P=0.014, r=0.541) and gastric cancer (P=0.002, r=0.625). A significant interaction was found between the effects of ERCC1 and BRCA1 mRNA expressions on sensitivity to cisplatin (P=0.010 for all patients;P=0.027 for gastric cancer patients).Conclusion:ERCC1 and BRCA1 mRNA expression levels correlated with ex vivo chemosensitivity of tumor cells to cisplatin in malignant pleural and peritoneal effusions. Detection of both ERCC1 and BRCA1 may have a higher reliability in predicting the sensitivity of tumor cells to cisplatin than detection of single ERCC1 or BRCA1 expression.

Malignant melanoma( MM) is a very malignant solid tumor that is highly invasive and has a poor prognosis. Al-though the treatment of advanced melanoma has entered the era of targeting and immunotherapy,chemotherapy is still not to be aban-doned. Chemotherapy for malignant melanoma has undergone a development process from single-drug chemotherapy,combination of two or three or even four drugs,and biochemotherapy. This article reviews the progress of chemotherapy for malignant melanoma,com-pares the main chemotherapy regimens,and looks forward into the future direction of chemotherapy.

[摘 要] 目的：探讨恶性黑色素瘤（malignant melanoma，MM）微环境分型对MM患者预后的评估价值。方法：对2010年7月至2017年5月在南京鼓楼医院手术切除的87例原发性MM组织进行二代测序，免疫组化法检测PD-1、PD-L1、CD3+ TIL、MSH2、MSH6、PMS2和MLH1的表达。随访患者的生存时间，分析不同免疫微环境分型对患者预后的影响及其基因表达特征。结果：根据PD-L1和TIL表达水平将87例MM患者的肿瘤微环境分为4个亚型：PD-L1+ TIL+型或双阳型（15/87，17.24%）、PD-L1+ TIL-型（15/87，17.24%）、PD-L1- TIL+型（20/87，22.99%）、PD-L1- TIL-型或双阴型（37/87，42.53%）。双阳型患者的中位无病生存期显著长于双阴型患者（P<0.05），此可能与双阴型患者存在更多CDK4、MCL1、MYC、AKT2、CCND1、FGF19等预后不良基因拷贝数扩增相关；双阳型患者PD-1表达显著高于双阴型患者（P<0.01），可能与PD-L1、TIL分别与PD-1呈共表达和共不表达有关。结论：根据PD-L1及TIL表达将MM 患者微环境分为4种亚型，能够区分MM患者预后，双阴型患者存在更多预后不良基因拷贝数扩增。

Objective: To evaluate the safety and efficacy of helical tomotherapy using simultaneously integrated boost and simultaneous integrated protection technique in the treatment of unresectable biliary tract cancers. Methods: The data of 23 patients with unresectable biliary tract cancer who received tomotherapy-based hypofractionated radiotherapy at Comprehensive Cancer Centre of Drum Tower Hospital,the Affiliated Drum Tower Clinical College of Nanjing Medical University between February 2015 and October 2017 were analyzed. There were 10 males and 13 females, aged from 40 to 85 years(median:58 years). Pathological type included intrahepatic cholangiocarcinomas(n=11), gallbladder cancers(n=6),extrahepatic cholangiocarcinomas(n=6). The irradiated sites covered primary tumors and areas of local invasion,including metastatic lymph nodes which were confined to the abdominal or retroperitoneal space. Dose escalation was achieved using simultaneously integrated boost(SIB) technique, and simultaneous integrated protection(SIP)technique was used to protect gastrointestinal tracts and other adjacent organs. Cox regression modal and Kaplan-Meier analysis were used to analyze the associations between patients′ characteristics and overall survival(OS). Results: The median total radiation dose was 54 Gy(range: 28-72 Gy)and median biologically effective dose(BED)was 74.4 Gy(range: 37.8-115.2 Gy).The median planning target volume(PTV)was 445.79 cm³(range:126.02-950.12 cm³). Based on the various PTV,patients received 2.4-6.0 Gy/fraction with 8-28 fractions. The local control rate was 65.2% and the median OS was 11.3 months(range:2.1-31.9 months).The most common cause of death was out-field failure and only 3 patients died of in-field failures. The longest survival was 31.9 months. BED≥70 Gy significantly improved OS,compared to BED<70 Gy(16.8 months vs.5.1 months)(HR=0.146, 95%CI:0.028-0.762, P=0.022). No patients developed grade ≥4 toxicities. Conclusions Helical tomotherapy-based hypofractionated radiotherapy is effective and well tolerated for patients with unresectable biliary tract cancer. The dose escalation with higher BED could improve the survival for such patients.