共查询到20条相似文献，搜索用时 15 毫秒
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Belinda L. Sun 《Clinical colorectal cancer》2021,20(1):e12-e20
Colorectal cancer (CRC) is the third most common cancer worldwide. In the past decade, mismatch repair deficiency (dMMR), manifested as microsatellite instability-high (MSI-H), has been recognized as a distinct mechanism promoting tumorigenesis in 15% of CRCs including 3% Lynch syndrome and 12% sporadic CRCs. As the molecular classifications of CRCs are continuously evolving, MSI-H CRCs appear to be the most homogeneous CRCs with distinct molecular, morphologic, and clinical features. MSI-H CRCs have dMMR causing MSI-H and genetic hypermutation but with diploid chromosomes. Morphologically, MSI-H CRCs appear as poorly differentiated or mucinous adenocarcinoma with characteristic lymphocytic infiltration. Most importantly, MSI-H CRCs have better stage-adjusted survival, do not respond well to standard 5-fluorouracil–based adjuvant chemotherapy, but do respond to immunotherapy. The United States Food and Drug Administration granted accelerated approval to immune checkpoint inhibitors, anti-programmed cell death protein-1 antibodies pembrolizumab and nivolumab, and the combination of nivolumab with anti-CTLA4 antibody ipilimumab for the second-line treatment of patients with stage IV MSI-H CRCs in 2017. There are still ongoing phase III clinical trials evaluating pembrolizumab and anti-programmed death-ligand 1 antibody atezolizumab as the first-line treatment in stage IV MSI-H CRCs and a phase I study on the combination of nivolumab and ipilimumab in patients with early stage CRC. These ongoing clinical studies on immunotherapy may lead to practice-changing results in the management of MSI-H CRCs. The National Comprehensive Cancer Network 2018 guidelines recommended MSI to be tested in all newly diagnosed CRCs. The MSI test will become increasingly vital in guiding adjuvant chemotherapy and immunotherapy in the management of CRCs. 相似文献
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The treatment approach to cervix cancer has remained unchanged for several decades and new therapeutic strategies are now required to improve outcomes, as the prognosis is still poor. In the last years, a better understanding of HPV tumor–host immune system interactions and the development of new therapeutics targeting immune checkpoints generated interest in the use of immunotherapy in cervix cancer. Preliminary phase I–II trials demonstrated the efficacy, the duration of responses and the manageable safety of this approach. Currently, many phase II and III studies are ongoing in both locally advanced and metastatic cervical cancer, assessing immunotherapy as a single agent or in combination with chemotherapy and radiotherapy. We reviewed the published data and the therapeutic implications of the most promising novel immunotherapeutic agents under investigation in cervix cancer. 相似文献
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Sarcomas are a heterogenous group of mesenchymal cancers comprising over 100 subtypes. Current chemotherapy for all but a very few subtypes has limited efficacy, resulting in 5-year relative survival rates of 16% for metastatic patients. While sarcomas have often been regarded as an “immune cold” tumor category, recent biomarker studies have confirmed a great deal of immune heterogeneity across sarcoma subtypes. Reports from the first generation of clinical trials treating sarcomas with immunotherapy demonstrate a few positive responses, supporting efforts to stratify patients to optimize response rates. This review summarizes recent advances in knowledge around immune biomarker expression in sarcomas, the potential use of new technologies to complement these study results, and clinical trials particularly of immune checkpoint inhibitor therapy in sarcomas.Each of the immune biomarkers assessed was reviewed for subtype-specific expression patterns and correlation with prognosis. Overall, there is extensive heterogeneity of immune biomarker presence across sarcoma subtypes, and no consensus on the prognostic effect of these biomarkers. New technologies such as multiplex immunohistochemistry and high plex in situ profiling may offer more insights into the sarcoma microenvironment. To date, clinical trials using immune checkpoint inhibitor monotherapy have not shown compelling clinical benefits. Combination therapy with dual checkpoint inhibitors or in combinations with other agents has yielded more promising results in dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma, angiosarcoma and alveolar soft-part sarcoma. Better understanding of the sarcoma immune status through biomarkers may help decipher the reasons behind differential responses to immunotherapy. 相似文献
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肺癌仍然是中国发病率和死亡率最高的恶性肿瘤,其中非小细胞肺癌（non-small cell lung cancer,NSCLC）约占80%以上。以靶向程序性死亡[蛋白]-1（programmed death protein-1,PD-1）或程序性死亡[蛋白]配体-1（programmed death ligand-1,PD-L1）的免疫检查点抑制剂（immune checkpoint inhibitor,ICI）为基础的治疗已成为了晚期肺癌的标准治疗手段之一。本综述将对晚期NSCLC免疫治疗的现状予以梳理,探讨现阶段面临的问题与挑战,并思考与展望未来发展方向。 相似文献
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Dwight H. Owen Lai Wei Erin M. Bertino Thomas Edd Miguel A. Villalona-Calero Kai He Peter G. Shields David P. Carbone Gregory A. Otterson 《Clinical lung cancer》2018,19(6):e893-e900
Background
The risk factors for immune-related adverse events (irAEs) remain undefined. Recently, a correlation between irAEs and clinical benefit was suggested. We examined the risk factors for irAEs and their effect on survival in patients with non–small-cell lung cancer (NSCLC) who had received immunotherapy.Patients and Methods
We performed a retrospective review of patients with NSCLC treated with single-agent immunotherapy at our institution. irAEs were determined by treating physician diagnosis. A landmark analysis was performed at 3 months using log-rank tests and the Bonferroni method.Results
irAEs occurred in 27 of 91 patients (30%). The median overall survival (OS) for patients with irAEs was longer than that for patients without (24.3 vs. 5.3 months; hazard ratio, 2.75; 95% confidence interval, 1.54-4.92; P < .001). However, a landmark analysis of patients after 3 months of treatment revealed no difference in OS between patients with and without irAEs. No increased risk of pneumonitis was seen in patients with previous thoracic radiotherapy, although these patients had shorter survival (4.2 vs. 9.7 months; P = .004). Radiotherapy after the initiation of immunotherapy (n = 15) did not increase the risk of irAEs or pneumonitis; however, these patients had improved OS (17.3 vs. 6.0 months; P = .016).Conclusion
The development of irAEs did not significantly correlate with survival when controlling for the duration of therapy in a landmark analysis. We found no increased risk of pneumonitis or irAEs in patients who had received radiotherapy. Radiotherapy before immunotherapy was associated with shorter survival, and radiotherapy after immunotherapy was associated with improved survival. 相似文献7.
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《Clinical breast cancer》2020,20(3):238-245
BackgroundThe purpose of this study was to investigate whether combining pembrolizumab with palliative radiation therapy (RT) improves outcomes in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC).Patients and MethodsEligible patients had HR+/human epidermal growth factor receptor 2-negative MBC; were candidates for RT to ≥ 1 bone, soft tissue, or lymph node lesion; and had ≥ 1 lesion outside the RT field. Patients received 200 mg pembrolizumab intravenously 2 to 7 days prior to RT and on day 1 of repeating 21-day cycles. RT was delivered to a previously unirradiated area in 5 treatments each of 4 Gy. The primary endpoint was objective response rate. The study used a 2-stage design: 8 women were enrolled into the first stage, and if at least 1 of 8 patients experienced an objective response, 19 more would be enrolled. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory endpoints included association of overall response rate with programmed death-ligand 1 status and tumor-infiltrating lymphocytes.ResultsEight patients were enrolled in stage 1. The median age was 59 years, and the median prior lines of chemotherapy for metastatic disease was 2. There were no objective responses, and the study was closed to further accrual. The median progression-free survival was 1.4 months (95% confidence interval, 0.4-2.1 months), and the median overall survival was 2.9 months (95% confidence interval, 0.9-3.6 months). All-cause adverse events occurred in 87.5% of patients, including just 1 grade 3 event (elevation of aspartate aminotransferase).ConclusionsRT combined with pembrolizumab did not produce an objective response in patients with heavily pre-treated HR+ MBC. Future studies should consider alternative radiation dosing and fractionation in patients with less heavily pre-treated HR+ MBC. 相似文献
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周凤格;易俊林 《中华放射肿瘤学杂志》2021,30(04):407-412
鼻咽癌是一种与EB病毒(EBV)感染密切相关的恶性肿瘤。鼻咽癌在接受现代调强放疗技术为主的综合治疗后,疗效得到进一步提高。提高高危患者和复发/远处转移鼻咽癌(R/M-NPC)患者的疗效成为治疗的主要目标。近年来,免疫治疗在肿瘤治疗领域不断取得进步。随着对EBV抗原及免疫检查点抑制剂的研究,免疫治疗在R/M-NPC治疗中取得了较大进展,免疫治疗联合放化疗将成为初治高危鼻咽癌临床研究的重点。 相似文献
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头颈部鳞癌(head and neck squamous cell carcinoma,HNSCC)是头颈部肿瘤的常见类型,其治疗水平有待提高。作为一种具有高度免疫缺陷的肿瘤,HNSCC主要机制包括免疫耐受的导入、局部的免疫逃逸和T细胞信号的破坏。免疫检查点是T细胞功能的重要决定因素,目前针对程序性细胞死亡1受体(programmed cell death 1,PD-1)的抑制剂得到了快速的发展。作为人源化的抗PD-1单克隆抗体,pembrolizumab和nivolumab均显示出针对复发或转移性HNSCC具有一定的解救治疗作用,进一步的研究值得期待。 相似文献
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背景与目的：激素抵抗型免疫检查点抑制剂相关心肌炎（steroid-resistant immune checkpoint inhibitor-associated myocarditis,srICIAM）是一种在接受免疫治疗后出现的心脏相关不良反应,患者总体预后较差。既往研究显示,包含Janus激酶（Janus kinase,JAK）抑制剂托法替布在内的免疫强化抑制治疗可能对srICIAM具有一定疗效。然而,由于缺乏足够的临床数据,其治疗效果及对于肿瘤病情的影响尚不明确。本研究旨在探讨托法替布对srICIAM的治疗效果。方法：本项回顾性病例对照研究连续纳入了2019年7月—2022年5月在复旦大学附属中山医院接受免疫检查点抑制剂治疗且出现srICIAM的36例恶性肿瘤患者。接受糖皮质激素联合托法替布治疗的患者被分配至托法替布组（n = 19）,未使用托法替布治疗的患者被分配至对照组（n = 17）。比较两组患者在临床特征、检验指标、影像学检查结果等方面的数据。同时对这些患者进行随访以监测心血管终点事件的发生。研究方案经过复旦大学附属中山医院伦理委员会批准（批准号：B2021-275R）。本研究按照《赫尔辛基宣言》的伦理学规范进行。结果：与对照组相比,在糖皮质激素累积剂量及持续时间差异无统计学意义（P>0.05）的情况下,托法替布组的心肌炎恢复时间更短（中位恢复时间：86.5 d vs 126.5 d,P = 0.021）。托法替布组的心肌炎相关死亡率显著低于对照组（5% vs 35%,P = 0.025）。结论：托法替布可在一定程度上降低srICIAM患者的死亡率并缩短康复时间,同时对于肿瘤患者的预后未产生不良影响。其可能成为srICIAM的潜在治疗药物之一。 相似文献
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A better knowledge of the complex interactions between cancer cells and the immune system has led to novel immunotherapy approaches. Treatment with selective anti-PD1, anti-PD-L1 and/or anti-CTLA-4 monoclonal antibodies (mAbs) has been a revolution in the therapeutic scenario of several cancer types, with the highest clinical efficacy in melanoma and in lung cancer. Colorectal cancer is one of the tumours in which immunotherapy has been shown less effective. Whereas in deficient mismatch repair (MMR) or in highly microsatellite instable (MSI-H) metastatic colorectal cancer there is clear clinical evidence for a therapeutic role of immune checkpoint inhibitors, the vast majority of patients with proficient MMR or with microsatellite stable (MSS) tumours do not benefit from immunotherapy. Defining the molecular mechanisms for immunogenicity in metastatic colorectal cancer is needed in order to develop predictive biomarkers and effective therapeutic combination strategies. A major challenge will be to identify, among the heterogeneous spectrum of this disease, those patients with specific tumour and tumour infiltrating stroma molecular and functional characteristics, that could be effectively treated with immunotherapy. In this review, we discuss the role of immune response in the context of metastatic colorectal cancer. We summarize the available clinical data with the use of anti PD-1/PD-L1 mAbs as single agents or in combination with anti CTLA-4 mAbs in MSI-H patients. Finally, we address the challenges and the potential strategies for rendering the more frequent microsatellite stable (MSS) tumours “immune-competent” and, therefore, amenable for effective immunotherapy interventions. 相似文献
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Leyre Zubiri Ian M. Allen Martin S. Taylor Amanda C. Guidon Steven T. Chen Sara R. Schoenfeld Tomas G. Neilan Meghan E. Sise Meghan J. Mooradian Krista M. Rubin Rebecca Karp Leaf Aparna R. Parikh Alexander Faje Justin F. Gainor Justine V. Cohen Florian J. Fintelmann Minna J. Kohler Michael Dougan Kerry L. Reynolds 《The oncologist》2020,25(3):e398-e404
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随着癌症生物学和发病机制研究的不断深入,免疫检查点抑制剂（ICIs）得以问世,为晚期肿瘤患者带来了新的生存希望,从而开启了癌症免疫治疗的新时代,但随着免疫治疗在临床上的广泛应用,免疫相关不良事件（irAEs）也逐渐显现出来,并广泛为一线临床医师所熟知。免疫检查点抑制剂可激活T细胞攻击体内的正常组织和器官,并导致多种不良反应。而免疫检查点抑制剂相关肺炎（CIP）是irAEs中较为罕见且预后较差的并发症之一。本文参考目前国内外相关文献,就部分ICIs的治疗机制及CIP的发病率、危险因素、发生机制、临床表现、影像学表现与CIP的分级及治疗管理作一综述。 相似文献
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