Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

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免疫检查点抑制剂在乳腺癌免疫治疗中应用进展

乳腺癌已成为全球发病率最高的癌症，其异质性使得乳腺癌分类治疗进入了精准治疗时代。随着肿瘤免疫治疗的成功，既往被认为“弱免疫原性”的乳腺癌也跨入了免疫治疗阶段。目前，免疫检查点抑制剂在乳腺癌免疫治疗的临床应用中取得了重大进展，但乳腺癌免疫治疗单药的获益人群有限，联合方案成为新的研究热点。随着免疫检查点抑制剂在乳腺癌中的研究进展，有效联合免疫治疗和化疗可能提高乳腺癌病人的生存率，但用药时机和适用人群仍需合理评估。免疫治疗在乳腺癌中既有应用前景，也存在挑战。     

High-performance multiplex drug-gated CAR circuits

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Tumor-induced erythroid precursor-differentiated myeloid cells mediate immunosuppression and curtail anti-PD-1/PD-L1 treatment efficacy

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Improving cancer-specific outcomes in solid organ transplant recipients: Where to begin?

In an article published in this issue of Cancer, D’Arcy et al link the incidence of cancer among recipients of solid organ transplantation (SOT) in the Scientific Registry of Transplant Recipients with data from regional and statewide cancer registries to examine cancer-specific mortality for common malignancies in SOT recipients. This analysis helps to illuminate the role of immune surveillance across a broad range of malignancies and compares the incidence of cancers due to virally mediated oncogenesis (lymphoma, squamous cell carcinoma of the aerodigestive epithelium, and hepatitis-induced liver cancer) with the incidence of other malignancies. The authors’ central finding is that cancer-specific mortality is significantly increased in SOT recipients in comparison with nontransplant recipients for multiple cancers, and the increased cancer incidence is not limited to the effects of viral oncogenesis. The authors document a significant increase in common epithelial malignancies that are currently treated with immune checkpoint antibodies, including melanoma, bladder cancer, colorectal cancer, cancers of the oral cavity/pharynx, kidney cancer, and lung cancer, and this supports the hypothesis that post-SOT immunosuppression affects immune surveillance in these cancers. Provocatively, the authors also document increases in the incidence and mortality of cancers not typically responsive to immune checkpoint therapies, including breast cancer and pancreatic cancer. The findings of D’Arcy et al suggest that immune surveillance controls oncogenesis and tumor progression in a broad range of malignancies and that breast cancer and pancreatic cancer could be sensitive to drugs targeting immune surveillance pathways other than those treated with currently Food and Drug Administration–approved antibodies to CTLA4 and PD-1/PD-L1.     

化疗周期数对DC/CIK治疗晚期非小细胞肺癌临床效果的影响

目的:研究化疗周期数对树突状细胞（DC）联合细胞因子活化的杀伤细胞（CIK）治疗晚期非小细胞肺癌（NSCLC）临床效果的影响。方法:回顾性分析2012年2至2016年2月内一科收治的124例化疗后接受DC/CIK治疗的晚期NSCLC患者的临床资料。患者按实际化疗周期分为2周期化疗组（43例）、3周期化疗组（40例）、4周期化疗组（41例）。3组患者临床资料及化疗方案相近。所有患者均在化疗后1~3个月内接受免疫细胞治疗。DC/CIK治疗前应用流式细胞仪检测外周血PD-1的表达。免疫细胞治疗完成后4周，参照RECIST标准和NCI-CTCAE 4.0标准评价近期临床疗效和安全性；根据卡氏（Karnofsky）功能状态评分评估患者生活质量（QOL）变化。结果:4周期化疗组PD-1表达水平明显高于2、3周期化疗组［(34.65±3.29)% vs (13.94±2.89)%和(25.88±5.06)%］，差异有统计学意义（P＜0.001）。2周期化疗组治疗的客观反应率（ORR）27.91%显著高于4周期化疗组（9.76%）（P＜0.05）。2周期化疗组疾病控制率(DCR)34.88%显著高于4 周期化疗组（14.63%），差异有统计学意义（P＜0.05）。2周期化疗组QOL改善率55.81%，显著高于3周期化疗（32.50%）、4周期化疗组（21.95%）（P＜0.05）。三组患者治疗后均未出现Ⅲ-Ⅳ级不良反应。结论:化疗周期数可降低DC/CIK对晚期非小细胞肺癌的临床治疗效果，化疗周期数越多病人取得DC/CIK细胞治疗的近期临床获益越小。