更新于：2024-09-19

Neuhauser Syndrome

Neuhauser综合征

更新于：2024-09-19

基本信息

别名

Cerebral palsy-hypotonic seizures-megalcornea syndrome、MEGALOCORNEA-MENTAL RETARDATION SYNDROME、MMR (megalocornea, mental retardation) syndrome

+ [22]

简介

A rare intellectual disability syndrome with most common characteristics of megalocornea, congenital hypotonia, varying degrees of intellectual disability, psychomotor/developmental delay, seizures, and mild facial dysmorphism (including round face, frontal bossing, antimongoloid slant of the eyes, epicanthal folds, large low set ears, broad nasal base, anteverted nostrils, and long upper lip). Interfamilial and intrafamilial clinical variability has been reported.

关联

项与 Neuhauser综合征相关的临床试验

NCT04428359 / CompletedN/A

A Comparative Study to Assess Efficacy of Intralesional MMR (Measles, Mumps, Rubella) Vaccine and Intralesional Vitamin D3 in Treatment of Warts

Common warts are papulonodular epidermal lesions caused by human papillomavirus (HPV) usually by the strains 1, 2, 4, 27 or 57. Cutaneous warts occur in 7% to 10% of the general population, with a maximum incidence between 12 and 16 years. There are multiple destructive treatment modalities of wart but they have many adverse effects. Hence immunotherapy is becoming popular in treatment of warts. It is believed that the injection to the HPV-infected tissue induces a strong nonspecific pro-inflammatory signal and attracts the antigen-presenting cells. Which then promotes a Th1 cytokine response and leads to delayed-type hypersensitivity reaction leading to the eradication of the HPV-infected cells.
We are undertaking a study to evaluate and compare the safety and efficacy of 2 such immunotherapeutic agents namely, IL measles, mumps and rubella (MMR) vaccine versus IL vitamin D3 for the treatment of warts.
RESEARCH HYPOTHESIS Null Hypotheses: IL MMR vaccine is not better than IL Vitamin D in the treatment of wart Alternative hypothesis: IL MMR vaccine is better than IL Vitamin D in the treatment of wart
Method: A total of 60 patients will be included in the study, 30 in each group. Group A and Group B patients will be injected with 0.5 ml of IL MMR and 0.5 ml of IL vitamin D3 respectively into a single or a maximum of 5 warts at a time in case of multiple warts. The IL injection will be given every 3 weeks for a maximum of 5 doses. Clinical assessment will be done by taking photographs and measurements at baseline, before each treatment session, and 3 months after the completion of treatment. The response will be evaluated by a decrease in the size and number of the wart(s) and photographic comparison. The response will be considered complete if there is a complete clearance of the wart(s), good if the wart(s) will regress in size by 75-99%, moderate if they regress by 50-74% and no or mild if there will be a 0-49% decrease in wart(s). Immediate and late side effects of MMR and Vitamin D will be evaluated after each session. Follow up will be made monthly for 3 months to detect any recurrence. Quality of life (QoL) will be measured in wart patients, using the Nepali version of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the end of follow up.
Statistical analysis will be done using Statistical Package for the Social Sciences 10.5 version.

开始日期2020-06-01

申办/合作机构

B.P. Koirala Institute of Health Sciences

NCT05129605 / RecruitingN/A

Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS)

This study aims to define the natural history of men at high genetic risk for prostate cancer on the basis of specific germline genetic mutations or a positive family history and evaluate the utility of prostate MRI as a screening tool. The hypothesis is that this targeted population of men are at elevated risk of developing prostate cancer compared to the general population, and enhanced screening with MRI will enable early detection and diagnosis of potentially aggressive prostate cancer, characterization of the penetrance of specific mutations, and potentially identify new genetic risk mutations.

开始日期2020-02-12

申办/合作机构

The General Hospital Corp.

IRCT138806252471N1 / CompletedN/A

Comparison of immunogenicity and short term reactogenicity of a local and a WHO approved commercial MMR vaccines in Iranian children and infants

开始日期2010-03-21

申办/合作机构-

100 项与 Neuhauser综合征相关的临床结果

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100 项与 Neuhauser综合征相关的转化医学

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0 项与 Neuhauser综合征相关的专利（医药）

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项与 Neuhauser综合征相关的文献（医药）

2023-11-10·European journal of cancer (Oxford, England : 1990)

Metastatic site and clinical outcome of patients with deficient mismatch repair metastatic colorectal cancer treated with an immune checkpoint inhibitor in the first-line setting.

Article

作者: Bahar Saberzadeh-Ardestani ; Jeremy C Jones ; Robert R McWilliams ; David Tougeron ; Thorvardur R Halfdanarson ; Rosine Guimbaud ; Joleen M Hubbard ; Clémence Fleccia ; Qian Shi ; Emily Alouani ; Mohamad B Sonbol ; Jonathan Ticku ; Zhaohui Jin ; Julien Taieb ; Frank A Sinicrope

PURPOSE:

Only one-half of deficient mismatch repair (d-MMR) metastatic colorectal cancers (mCRC) demonstrate durable responses to immune checkpoint inhibitors (ICIs). Given preclinical data indicating that liver metastases sequester activated CD8⁺ T cells from systemic circulation, we examined clinical outcome by metastatic site.

PATIENTS AND METHODS:

In a retrospective cohort of patients with d-MMR mCRCs treated at multiple centers in France (n = 66), we sought to validate data from a U.S. cohort, and performed pooled analysis (n = 104). All patients received first-line ICI monotherapy. Metastatic site was analyzed in relationship to tumor response (RECIST version 1.1), and with progression-free survival (PFS) by multivariable stratified Cox regression after adjustment for covariates.

RESULTS:

Objective responses were achieved in 38/66 (58%) of patients in the validation cohort. Best tumor response included 13 (20%) complete responses (CR), 25 (38%) partial responses (PR), 16 (25%) stable disease, and 11 (17%) progressive disease (PD). One-year and 5-year PFS rates were 73% and 67%, respectively; 18 (27%) patients progressed during immunotherapy. Best tumor response was attenuated in patients with liver metastasis (P = 0.03). Presence of liver metastasis, but not other sites, was associated with significantly poorer PFS after adjustment for covariates (HR_adj 2.82; 95%CI, 1.08-7.39; P_adj=0.03). In a pooled analysis, liver metastasis remained significantly and independently associated with poorer PFS (HR_adj 3.18; 95%CI, 1.52-6.67; P_adj=0.002) and with attenuated tumor best response (P = 0.01).

CONCLUSIONS:

Metastasis to the liver, but not other sites, was validated as an independent factor associated with poorer response and survival after ICI treatment in d-MMR mCRCs. These data underscore the need for novel therapeutic strategies in these patients.

2022-04-02·Endocrine3区 · 医学

Correlation of mismatch repair deficiency with clinicopathological features and programmed death-ligand 1 expression in thyroid carcinoma.

3区 · 医学

Article

作者: Pei-Pei Qiao ; Kai-Sai Tian ; Li-Tao Han ; Ben Ma ; Cen-Kai Shen ; Run-Yu Zhao ; Yi Zhang ; Wen-Jun Wei ; Xiao-Ping Chen

BACKGROUND:

Mutations in DNA mismatch repair (MMR) genes associated with thyroid carcinoma (TC) have rarely been reported, especially in East Asian populations.

METHODS:

We examined tumor tissue from a cohort of 241 patients diagnosed with TC between 2008 and 2020. MMR proteins were detected using tissue microarray-based immunohistochemistry in order to identify MMR-protein-deficient (MMR-D) and MMR-protein-intact (MMR-I) tumors. We retrospectively summarized the clinicopathologic characteristics of patients with MMR-D TC, measured the expression of PD-L1, and recorded overall survival (OS) and other clinical outcomes.

RESULTS:

In our cohort, there were 18 (7.5%) MMR-D (MLH1, MSH2, MSH6, and PMS2) patients, including 12 with papillary TC (PTC) (6.7%), 2 with poorly differentiated TC (PDTC) (4.7%), and 4 with anaplastic TC (ATC) (22.2%). Half of them (9/18) showed a specific deletion in MSH6, and 6 of them also carried variants in the MSH6 and PMS2 gene. Survival was significantly better in patients with MMR-D ATC than in those with MMR-I tumors (p = 0.033). Four of the 18 MMR-D patients (22%) were found to be PD-L1 positive. Their OS was much shorter than that of PD-L1-negative patients.

CONCLUSIONS:

MMR-D and PD-L1 positivity appear to be associated with clinicopathological characteristics and prognosis in TC. The results indicate that MMR status may have important prognostic significance in TC. Therefore, immune checkpoint inhibitors that target the PD-1/PD-L1 pathway may be a treatment option for TCs.

2022-01-01·Indian journal of thoracic and cardiovascular surgery

A rare case of Neuhauser syndrome associated with a Kommerell diverticulum.

Article

作者: Nabil Dib ; Thibaut Lapotre ; Jacques Tomasi ; Nabila El Gueddari ; Amedeo Anselmi ; Bertrand Richard de laTour ; Jean-Philippe Verhoye

Neuhauser syndrome is a rare vascular anomaly characterized by the esophagus and trachea circling via the ligamentum arteriosum and right aortic arch. Kommerell's diverticulum have the same characteristic by an outpouch at the onset of an aberrant left subclavian artery worsening this compression. The association between these pathologies is very rare and the operative strategy is unclear. We describe a case with the association with a computed tomography scanner aortic reconstruction and a repair's operative strategy.

项与 Neuhauser综合征相关的新闻（医药）

2024-01-03

·奇点网

高通量测序技术的逐渐普及，帮助更多患者得到适合的治疗。

*仅供医学专业人士阅读参考对于具有错配修复缺陷（MMR-D）的癌症患者而言，免疫检查点抑制剂治疗是一种非常有效的治疗方法。准确评估MMR状态对于治疗决策至关重要，因为假阴性会限制免疫检查点抑制剂的使用，从而降低患者的临床获益。近日，美国布列根和妇女医院的Amin H. Nassar及其同事们发表在《癌细胞》期刊上的论文[1]，揪出了当前指南中MMR标准检测方法的漏洞，并提供了能够帮助更多乳腺癌患者从免疫治疗中获益的方法。他们结合下一代测序技术（NGS）的检测结果发现，采用当前推荐的免疫组化染色（IHC）方法检测MMR-D时，有5.9%的子宫内膜癌患者和1%的结直肠癌患者被漏诊，而NGS可以识别出这些患者并帮助其接受更为有效的免疫治疗。据估计，如果采用NGS进行MMR检测，可额外识别出5000多名被IHC漏诊的美国结直肠癌或子宫内膜癌患者。这项研究结果支持重新评估指南中以IHC作为MMR标准检测方法的建议，并提出采用更加灵敏的NGS在诊断早期阶段进行MMR检测。论文首页截图DNA错配修复系统（MMR）在细胞中负责识别和修复DNA复制过程中产生的错误，维持遗传稳定性。当发生错配修复缺陷（MMR-D）时，常常引起DNA中的短串联重复序列长度改变，即微卫星不稳定性（MSI），并且与多种癌症的发展有关，特别是与结直肠癌和子宫内膜癌的关系最为密切。MMR的常用检测方法为两种，一种是通过免疫组化染色（IHC）检测肿瘤组织中MMR蛋白（MLH1、MSH2、MSH6、PMS2）的异常表达，另一种是通过聚合酶链反应（PCR）检测MSI。目前，美国病理学会（CAP）、美国临床肿瘤协会（ASCO）、欧洲肿瘤医学学会（ESMO）推荐，将IHC作为结直肠癌或子宫内膜癌患者进行MMR检测的首选方法[2,3]。ESMO推荐在不同癌症类型和免疫治疗疗程中进行MSI检测[3]下一代测序（NGS）又称高通量测序技术，能够快速、全面地检测和分析MMR-D所导致的MSI。此次研究共纳入1655名结直肠癌或子宫内膜癌患者，这些患者的MMR状态由IHC和NGS进行检测。对比两种方式，Amin H. Nassar等人发现，5.9%的子宫内膜癌患者和1%的结直肠癌患者，其IHC的检测结果为错配修复功能正常，而NGS检测结果为MMR-D。进一步分析结果显示，这些被IHC漏诊、而被NGS检测为MMR-D的患者，对免疫治疗的反应比其它全身治疗明显更好，具有更长的生存期。另外，与NGS和IHC结果一致为错配修复功能正常的患者相比，这些患者接受免疫检查点治疗的中位总生存期和治疗失败时间显著延长（中位OS：NR[95%CI 10个月-NR] vs 14.9个月[95%CI 7.3-25]，p=0.003）（中位TTF：44.4个月[95%CI 10-NR] vs 5.0个月[95%CI 3.2-7.3],p=0.001），而与NGS、IHC检测结果一致为MMR-D的患者免疫检查点抑制剂疗效相近。这意味着，NGS可以更灵敏地检测MMR状态，并使具有MMR-D的结直肠癌患者或子宫内膜癌者不会错过对其更为有效的免疫治疗。据统计，2022年美国新发结直肠癌和新发子宫内膜癌分别达到151030例和65950例。按此推断，仅以IHC作为检测方法，其中共有5401名具有MMR-D的患者被漏诊，而NGS检测可以识破IHC的假阴性结果。“我们不想错过这些患者，否则可能会剥夺他们获得长期治疗益处的机会，”Amin H. Nassar表示[4]。“此外，我们也希望能够为不同患者提供适合的治疗方式，避开毒性更大或效果较差的疗法。”随着NGS技术已经越来越多地被用于日常临床护理中，研究者们建议在诊断早期阶段采用NGS进行MMR检测，以及早识别漏诊的MMR-D患者，指导其采取适当的临床决策。接下来，他们将在更大队列中验证这一结论，并探索基于NGS的MMR检测方法是否同样有助于指导其它癌症类型患者的治疗。参考文献：[1]https://www-cell-com.libproxy1.nus.edu.sg/cancer-cell/fulltext/S1535-6108(23)00420-8[2]Vikas, P., Messersmith, H., Compton, C.,Sholl, L., Broaddus, R.R., Davis, A., EstevezDiz, M., Garje, R., Konstantinopoulos, P.A.,Leiser, A., et al. (2023). Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: ASCO Endorsement of College of American Pathologists Guideline. J. Clin. Oncol. 41, 1943–1948.[3]Luchini, C., Bibeau, F., Ligtenberg, M.J.L., Singh, N., Nottegar, A., Bosse, T., Miller, R., Riaz, N., Douillard, J.Y., Andre, F., and Scarpa, A. (2019). ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann. Oncol. 30, 1232–1243.[4]https://www.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=4618本文作者丨张艾迪

ASCO会议免疫疗法临床研究临床结果

2023-10-16

·PRNewswire

New Study Demonstrates Lunit SCOPE IO's Effectiveness to Predict Biliary Tract Cancer Therapy Outcomes - Findings to be Presented at the ESMO 2023

- Nine abstracts, featuring the effectiveness of Lunit's AI-powered TIL/WSI analyzer and biomarker platform, accepted by the ESMO 2023 Congress SEOUL, South Korea, Oct. 16, 2023 /PRNewswire/ -- Lunit (KRX:328130.KQ), a leading provider of AI-powered solutions for cancer diagnostics and therapeutics, today announced the presentation of 9 studies at the upcoming European Society for Medical Oncology (ESMO) 2023 Congress, to be held in Madrid, Spain, from October 20-24. Continue Reading Lunit AI-powered TIL analyzer, Lunit SCOPE IO (PRNewsfoto/Lunit) During this year's congress, Lunit plans to highlight the predictive value and analytical power of its Lunit SCOPE suite, offering valuable insights for understanding the tumor microenvironment, predicting treatment responses, and accurately assessing HER2 scores, in various types of cancer such as biliary tract cancer, head and neck squamous cell carcinoma, and non-small cell lung cancer. A collaborative study indicated that AI-based immune phenotyping can predict therapy outcomes in advanced biliary tract cancer (BTC) patients who are planning to be treated with anti-PD-1 therapy. A total of 337 H&E-stained whole slide images (WSI) were acquired for assessment. In the study, the research team defined the immune phenotype of the WSI samples via Lunit SCOPE IO, Lunit's AI TIL (tumor-infiltrating lymphocytes) analyzer. Among the three immune phenotypes (inﬂamed; immune-excluded; immune-desert), the inflamed group showed enhanced overall survival (12.5 vs. 5.1 months), progression-free survival (5.0 vs. 2.0 months), and objective response rates (27.5% vs. 7.7%), compared to the non-inflamed group. In another study, it was found that TIL density in tumor microenvironment is highly correlated with favorable treatment response to immune checkpoint inhibitor (ICI) in head and neck squamous cell carcinoma (HNSCC). Assessed by Lunit SCOPE IO, patients with high-TIL showed a higher objective response rate (21.6% vs 5.7%) and more favorable median progression-free survival (3.2 vs 1.6 months). Lunit also plans to present the results of three trials during this year's congress. A joint trial with the Mayo Clinic unveils that epithelial TIL demonstrated the highest ability to distinguish between MMR-D (Mismatch repair deficiency) and MMR-P (Mismatch repair proficiency) tumors in colon cancer. The post-hoc exploratory analysis results of three clinical trials utilizing Lunit SCOPE IO in Italy and France are also set to be showcased. In another study, HER2 (human epidermal growth factor receptor-2) scoring in biliary tract cancer was evaluated using Lunit SCOPE HER2. The analysis showed a substantial concordance of 75.3% between AI and human pathologists' assessments. Another study aimed to predict multiple druggable mutations in non-small cell lung cancer (NSCLC) based on AI analysis of H&E images. More than 3,000 NSCLC samples were used as training data to develop an AI-powered predictive model. In validation in an independent dataset, the model showed robust performance in predicting six types of mutations (EGFR-mt, KRAS-mt, ALK-tr, ROS1-tr, RET-tr, MET-ex). Notably, for MET exon skipping mutations, the model achieved a high positive predictive value (PPV), showing that test-positive patients were three times more likely to have true-MET-ex positive mutations compared to the overall patient population. Moreover, specificity and PPV for identifying patients without mutations (All-WT) were 99.2% and 95.2% respectively, which means with AI assistance unnecessary tests can be avoided. Following the results, it is expected that the newly developed AI genotype predictor, available for multiple genotypes in non-small cell lung cancer, holds immense potential for widespread adoption by clinicians and pharmaceutical industry leaders globally. "We are thrilled to be at this year's ESMO with nine groundbreaking study results that prove the effectiveness of the Lunit SCOPE AI WSI analyzer and biomarker platform," said Brandon Suh, CEO of Lunit. "The study results emphasize the substantial progress made with Lunit SCOPE IO, building compelling evidence of the critical role of immune phenotyping in understanding cancer biology and optimizing treatment strategies. We remain committed to advancing this transformative technology through further research and development." For inquiries or to schedule a meeting with the Lunit team, please contact [email protected]. Lunit's Abstracts at ESMO 2023 About Lunit Lunit is a deep learning-based medical AI company on a mission to conquer cancer. Our focus is on developing AI solutions for precision diagnostics and therapeutics, ensuring the right diagnosis, and treatment, at the right cost for each patient. Lunit is devoted to developing advanced medical image analytics and AI-based biomarkers via cutting-edge technology. Founded in 2013, Lunit has been acknowledged around the world for its advanced, state-of-the-art technology and its application in medical images. As a medical AI company grounded on clinical evidence, the company's findings are presented in major peer-reviewed journals, such as the Journal of Clinical Oncology and JAMA Network Open, and global conferences, including ASCO and AACR. After receiving FDA clearance and the CE Mark, our flagship Lunit INSIGHT suite is clinically used in approximately 2,000+ hospitals and medical institutions across 40+ countries. Lunit is headquartered in Seoul, South Korea, with offices and representatives worldwide. For more information, please visit lunit.io About Lunit SCOPE Lunit SCOPE is a suite of AI-powered software that analyzes tissue slide images for digital pathology and AI biomarker development, aiming to optimize workflow and facilitate more accurate and predictive clinical data for clinicians and researchers. Lunit SCOPE platform offers multiple AI-powered tissue analysis products and assays that can streamline digital pathology workflow and diagnostics and enhance the drug development process. Lunit SCOPE IO analyzes the tumor microenvironment (TME) based on H&E analysis and provides AI-based predictive clinical outcome information. In addition, AI-driven Immunohistochemistry (IHC) slide analysis services are offered, through products such as Lunit SCOPE PD-L1, Lunit SCOPE HER2, Lunit SCOPE ER/PR, and others. SOURCE Lunit

临床结果免疫疗法

2023-05-16

·生物谷

Cancer Cell：邓艳红团队通过单细胞RNA测序，揭示PD-1疗法成功治疗结直肠癌的机制

这些研究结果为免疫检查点抑制剂（ICI）成功治疗的机制和提高治疗效果的潜在靶点提供了宝贵的资源和生物学见解。结直肠癌（Colorectal Cancer，CRC）是全世界范围内发病率第三的癌症，每年新增发病人数近200万（仅次于乳腺癌和肺癌），每年导致的死亡人数接近100万（仅次于肺癌）。大约每25个人就有1人会在其一生中患上结直肠癌。而在我国，结直肠癌年发病人数仅次于肝癌，2020年新增56万结直肠癌患者。更重要的是，近30年来，50岁以下的年轻人群中结直肠癌的发病率一直在上升。错配修复缺陷和微卫星不稳定性高（d-MMR/MSI-H）代表了一种独特的生物标志物定义的癌症群体，约占所有结直肠癌（CRC）的15%。相比错配修复熟练和微卫星稳定（pMMR/MSS）的结直肠癌，错配修复缺陷和微卫星不稳定性高（d-MMR/MSI-H）的结直肠癌具有更高的肿瘤新抗原负荷和更密集的免疫细胞浸润，这表明免疫检查点抑制剂（ICI）疗法对其更具益处。临床数据也证实了这一点，靶向PD-1/PD-L1通路的免疫检查点抑制剂对错配修复缺陷和微卫星不稳定性高（d-MMR/MSI-H）患者非常有效。然而，有高达50%的转移性错配修复缺陷和微卫星不稳定性高（d-MMR/MSI-H）结直肠癌患者对免疫治疗具有耐药性，因此，亟需解决与免疫检查点抑制剂（ICI）治疗相关的挑战，以提高当前治疗方案的疗效。 2023年5月11日，中山大学附属第六医院邓艳红团队在 Cancer Cell 期刊发表了题为：Remodeling of the immune and stromal cell compartment by PD-1 blockade in mismatch repair-deficient colorectal cancer 的研究论文。该研究阐明了免疫检查点抑制剂（ICI）治疗期间的关键免疫细胞和基质细胞亚群的动态变化，并为错配修复缺陷和微卫星不稳定性高（d-MMR/MSI-H）结直肠癌患者对PD-1阻断疗法的不同反应的细胞基础提供了新的见解。该研究也提供了炎症和免疫检查点抑制剂（ICI）诱导的治疗反应之间关联的证据。这项研究为免疫检查点抑制剂（ICI）成功治疗的机制和提高治疗效果的潜在靶点提供了宝贵的资源和生物学见解。免疫检查点抑制剂（ICI）治疗完全缓解的潜在机制尚未完全了解，这阻碍了目前对错配修复缺陷和微卫星不稳定性高（d-MMR/MSI-H）结直肠癌治疗效果和方案的改进。来自bulk RNA测序和多重免疫荧光的基因表达特征的新证据表明，免疫检查点抑制剂（ICI）的疗效在很大程度上取决于肿瘤免疫微环境（TIME）。之前有研究显示，错配修复缺陷和微卫星不稳定性高（d-MMR/MSI-H）结直肠癌对PD-1抑制剂的反应与肿瘤突变负荷无关，而与高克隆扩增的T细胞有关。此外，错配修复缺陷（d-MMR）结直肠癌在免疫检查点抑制剂（ICI）治疗后CD3+T细胞和CD8+T细胞浸润以及干扰素-γ值显著升高。然而，这些研究主要依赖于对大量肿瘤的测量分析技术，这限制了它们捕捉细胞异质性和全面探索免疫成分或细胞相互作用变化的能力。单细胞RNA测序（scRNA-seq）的最新进展为在细胞分辨率上探索免疫检查点抑制剂（ICI）治疗反应中的细胞类型特异性模式和相互作用提供了新途径。最近已有研究团队发表了免疫治疗后实体瘤（例如乳腺癌、黑色素瘤）中肿瘤免疫微环境（TIME）的单细胞分析研究，但尚不清楚如何将这些发现应用于结直肠癌免疫治疗的研究。特别是，还没有结直肠癌免疫治疗前后的单细胞分析研究发表。在这篇发表在 Cancer Cell 的最新研究中，邓艳红团队首次从前瞻队列中对PD-1抑制剂（特瑞普利单抗，君实生物研发）或特瑞普利单抗与COX-2抑制剂（塞来昔布）联用治疗的错配修复缺陷和微卫星不稳定性高（d-MMR/MSI-H）结直肠癌患者的细胞群进行了深入的细胞和分子层面的分析。该研究旨在揭示术后残余肿瘤的患者对免疫检查点抑制剂（ICI）治疗的耐药性和敏感性的基础，并提示ICI的潜在治疗靶点。研究团队比较了实现病理完全缓解（pCR）的患者在免疫检查点抑制剂（ICI）治疗前后的细胞类型分布和功能变化，以阐明ICI治疗成功的相关机制。研究团队还分析了pCR和非pCR反应在治疗动力学上的差异，以探讨免疫治疗耐药的机制。具体来说，研究团队利用单细胞RNA测序技术（scRNA-seq）研究了19例接受新辅助PD-1阻断疗法的错配修复缺陷和微卫星不稳定性高（d-MMR/MSI-H）结直肠癌患者的免疫细胞和基质细胞的动态。结果显示，在病理完全缓解（pCR）的肿瘤中，治疗后CD8+Trm-mitotic、CD4+Tregs、促炎IL1b+Mono和CCL2+成纤维细胞的比例一致下降，而CD8+Tem、CD4+Th、CD20+B和HLA-DRA+内皮细胞的比例增加。肿瘤微环境中的促炎特征通过调节CD8+T细胞和其他反应相关的免疫细胞群介导残留肿瘤的持续存在。这些研究结果为免疫检查点抑制剂（ICI）成功治疗的机制和提高治疗效果的潜在靶点提供了宝贵的资源和生物学见解。