更新于：2024-09-19

GATA6

更新于：2024-09-19

基本信息

别名

GATA binding protein 6、GATA-binding factor 6、GATA6

+ [1]

简介

Transcriptional activator (PubMed:19666519, PubMed:27756709, PubMed:22750565, PubMed:22824924). Regulates SEMA3C and PLXNA2 (PubMed:19666519). Involved in gene regulation specifically in the gastric epithelium (PubMed:9315713). May regulate genes that protect epithelial cells from bacterial infection (PubMed:16968778). Involved in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression (By similarity). Binds to BMP response element (BMPRE) DNA sequences within cardiac activating regions (By similarity). In human skin, controls several physiological processes contributing to homeostasis of the upper pilosebaceous unit. Triggers ductal and sebaceous differentiation as well as limits cell proliferation and lipid production to prevent hyperseborrhoea. Mediates the effects of retinoic acid on sebocyte proliferation, differentiation and lipid production. Also contributes to immune regulation of sebocytes and antimicrobial responses by modulating the expression of anti-inflammatory genes such as IL10 and pro-inflammatory genes such as IL6, TLR2, TLR4, and IFNG. Activates TGFB1 signaling which controls the interfollicular epidermis fate (PubMed:33082341).

关联

100 项与 GATA6 相关的临床结果

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100 项与 GATA6 相关的转化医学

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0 项与 GATA6 相关的专利（医药）

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1,209

项与 GATA6 相关的文献（医药）

2024-11-01·Translational Research

Transcriptome-based classification to predict FOLFIRINOX response in a real-world metastatic pancreatic cancer cohort

Article

作者: Dijk, Frederike ; van Laarhoven, Hanneke W M ; Lansbergen, Marjolein F ; Dings, Mark P G ; Hooijer, Gerrit K J ; Manoukian, Paul ; Koster, Jan ; Bijlsma, Maarten F ; Zwijnenburg, Danny A ; Verheij, Joanne ; Waasdorp, Cynthia ; Wilmink, Johanna W ; Fariña, Arantza ; Medema, Jan Paul

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at metastatic stage and typically treated with fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX). Few patients benefit from this treatment. Molecular subtypes are prognostic in particularly resectable PDAC and might predict treatment response. This study aims to correlate molecular subtypes in metastatic PDAC with FOLFIRINOX responses using real-world data, providing assistance in counselling patients. We collected 131 RNA-sequenced metastatic biopsies and applied a network-based meta-analysis using published PDAC classifiers. Subsequent survival analysis was performed using the most suitable classifier. For validation, we developed an immunohistochemistry (IHC) classifier using GATA6 and keratin-17 (KRT17), and applied it to 86 formalin-fixed paraffin-embedded samples of advanced PDAC. Lastly, GATA6 knockdown models were generated in PDAC organoids and cell lines. We showed that the PurIST classifier was the most suitable classifier. With this classifier, classical tumors had longer PFS and OS than basal-like tumors (PFS: 216 vs. 78 days, p = 0.0002; OS: 251 vs. 195 days, p = 0.049). The validation cohort showed a similar trend. Importantly, IHC GATA6^low patients had significantly shorter survival with FOLFIRINOX (323 vs. 746 days, p = 0.006), but no difference in non-treated patients (61 vs. 54 days, p = 0.925). This suggests that GATA6 H-score predicts therapy response. GATA6 knockdown models did not lead to increased FOLFIRINOX responsiveness. These data suggest a predictive role for subtyping (transcriptomic and GATA6 IHC), though no direct causal relationship was found between GATA6 expression and chemoresistance. GATA6 immunohistochemistry should be seamlessly added to current diagnostics and integrated into upcoming clinical trials.

2024-11-01·Translational Oncology

Metavert synergises with standard cytotoxics in human PDAC organoids and is associated with transcriptomic signatures of therapeutic response

Article

作者: Ei, Shigenori ; Wolf, Stephan ; Brors, Benedikt ; Zhou, Xu ; Bergmann, Frank ; Lim, Adrian ; Mughal, Sadaf S. ; Schulz, Angela ; Hulkkonen, Johannes ; Beyer, Georg ; An, Jingyu ; Michalski, Christoph W ; Hu, Kai ; Springfeld, Christoph ; Mayerle, Julia ; Pandol, Stephen J ; Zezlina, Lenart ; Neoptolemos, John P. ; Büchler, Markus W ; Mehrabi, Arianeb ; Edderkaoui, Mouad ; Mughal, Sadaf S ; Hackert, Thilo ; Pandol, Stephen J. ; Al-Saeedi, Mohammed ; Fortunato, Franco ; Roth, Susanne ; Merz, Daniela ; Peccerella, Teresa ; Loos, Martin ; Michalski, Christoph W. ; Büchler, Markus W. ; Kurilov, Roma ; Bailey, Peter ; Pfütze, Katrin ; Neoptolemos, John P

BACKGROUNDDespite some recent advances, pancreatic ductal adenocarcinoma (PDAC) remains a growing oncological challenge. New drugs capable of targeting more than one oncogenic pathway may be one way to improve patient outcomes. This study characterizes the effectiveness of Metavert a first-in-class dual inhibitor of GSK3-β and histone deacetylase in treating PDAC as a single agent or in combination with standard cytotoxics.METHODSThirty-six Patient-Derived Organoids (hPDOs) characterised by RNASeq and whole exome sequencing were treated with Metavert alone or in combination with standard cytotoxics. Transcriptomic signatures (TS) representing sensitivity to Metavert alone or sensitivity to Metavert + irinotecan (IR) were evaluated in 47 patient samples, chemo-naïve in 26 and post-chemotherapy in 21 (gemcitabine=5; FOLFIRINOX=14, both=2) with companion multiplexed immunofluorescence and RNASeq data.RESULTSMetavert combined with gemcitabine, irinotecan, 5FU, oxaliplatin, and paclitaxel was synergistic in the hPDOs. Basal-subtype hPDOs were more sensitive to Metavert alone whereas the Metavert+IR combination exhibited synergy in Classical-subtype hPDOs with increased apoptosis and autophagy. hPDO-derived TS evaluated in PDAC tissues demonstrated that Metavert-TS^Hi samples were enriched for mRNA splicing and DNA repair processes; they were associated with Basal-like tissues but also with GATA6^+ve-chemo-naïve samples and were higher following gemcitabine but not FOLFIRINOX treatment. In contrast, Metavert+IR-TS^HI samples were enriched for TP53 pathways; they were associated with Classical-like pretreatment samples and with GATA6^+ve/KRT17^+ve hybrid cell types following FOLFIRINOX, but not gemcitabine treatment, and were unrelated to transcriptional subtypes.CONCLUSIONSMetavert as a single agent and in combination with irinotecan offers novel strategies for treating pancreatic cancer.

2024-09-01·Development

Gata6 functions in zebrafish endoderm to regulate late differentiating arterial pole cardiogenesis

Article

作者: Torregroza, Ingrid ; Evans, Todd ; Sam, Jessica

ABSTRACTMutations in GATA6 are associated with congenital heart disease, most notably conotruncal structural defects. However, how GATA6 regulates cardiac morphology during embryogenesis is undefined. We used knockout and conditional mutant zebrafish alleles to investigate the spatiotemporal role of gata6 during cardiogenesis. Loss of gata6 specifically impacts atrioventricular valve formation and recruitment of epicardium, with a prominent loss of arterial pole cardiac cells, including those of the ventricle and outflow tract. However, there are no obvious defects in cardiac progenitor cell specification, proliferation or death. Conditional loss of gata6 starting at 24 h is sufficient to disrupt the addition of late differentiating cardiomyocytes at the arterial pole, with decreased expression levels of anterior secondary heart field (SHF) markers spry4 and mef2cb. Conditional loss of gata6 in the endoderm is sufficient to phenocopy the straight knockout, resulting in a significant loss of ventricular and outflow tract tissue. Exposure to a Dusp6 inhibitor largely rescues the loss of ventricular cells in gata6−/− larvae. Thus, gata6 functions in endoderm are mediated by FGF signaling to regulate the addition of anterior SHF progenitor derivatives during heart formation.

项与 GATA6 相关的新闻（医药）

2024-06-27

·生物探索

Cell | 揭示原始内胚层多能性：重塑胚胎发育的新途径

引言在哺乳动物的早期胚胎发育过程中，囊胚的形成涉及外胚层（trophectoderm，TE）的特化，随后内细胞团（inner cell mass，ICM）分化为胚胎上皮细胞（epiblast，Epi）和原始内胚层（primitive endoderm，PrE）。这一过程中，胚胎保持了一段时间的多能性（plasticity），即在实验条件下，细胞能够重新定位其命运。6月24日Cell杂志的报道“The primitive endoderm supports lineage plasticity to enable regulative development”，发现单独的PrE细胞就足以再生出完整的囊胚，并继续植入后的发育。研究人员在体外鉴定了一种与早期PrE相似的细胞群体，这些细胞群体展示了相同的胚胎和胚外的多能性，能够形成完整的干细胞模型——称为胚样体（blastoids）。PrE细胞的分化受JAK/STAT信号通路的抑制，同时OCT4的持续表达以及一部分多能性相关转录因子的表达，维持了一种允许多谱系分化的增强子（enhancer）景观。该研究表明，转录因子的持续存在是调控发育中多能性的基础，并强调了PrE在受干扰发育中的重要性。该研究为理解胚胎早期发育中的细胞多能性机制提供了新的见解，并揭示了PrE在再生胚胎发育过程中的关键作用。这些发现不仅挑战了传统观点，即PrE只是简单的支持组织，还表明它在胚胎发育的调节性过程中发挥了重要作用。通过深入研究PrE的分子基础和其在多能性维持中的作用，可以更好地理解胚胎发育的复杂性及其潜在的应用前景。在哺乳动物胚胎发育的早期阶段，胚胎细胞的命运并非一成不变。2细胞阶段的胚胎细胞（blastomere）能够从单个细胞生成一个完整的有机体，随着发育的进行，每个胚胎细胞的潜能逐渐受到限制。胚胎在囊胚形成阶段，ICM中的细胞在成纤维细胞生长因子（fibroblast growth factor，FGF）和细胞外信号调节激酶（extracellular signal-regulated kinase，ERK）的作用下，分化为Epi或PrE。Epi最终发育成胚胎本身，而PrE则发育成视网膜内胚层（visceral endoderm，VE）和壁内胚层（parietal endoderm，PE）。为了探索原始内胚层（primitive endoderm, PrE）在哺乳动物早期胚胎发育中的多能性（plasticity），研究人员进行了多项关键实验。这些实验不仅帮助我们理解PrE的特性，还揭示了其在胚胎发育过程中的调控机制。胚胎处理研究人员将8细胞阶段的胚胎分成两组，分别用成纤维细胞生长因子4（FGF4）和MEK抑制剂PD0329501（PD03）处理24小时，以转化为PrE或Epi。处理后，通过免疫手术去除外胚层（trophectoderm, TE），并在不同条件下培养这些胚胎。细胞标记和确认使用GATA6和NANOG作为PrE和Epi细胞的标记物，分别确认处理后的内细胞团（inner cell mass, ICM）细胞类型。通过免疫荧光染色和细胞计数，评估不同处理条件下ICM中PrE和Epi细胞的比例。体外培养和验证从小鼠胚胎干细胞（embryonic stem cells, ESCs）分化得到PrE细胞，然后在含有白血病抑制因子（LIF）、Wnt和转化生长因子β（TGF-β）信号的培养基中扩展为原始额外胚层干细胞（naive extra-embryonic endoderm, nEnd）。在三维培养条件下，观察nEnd细胞自发形成具有内外层结构的球体，外层为GATA6阳性细胞，内层为SOX2阳性细胞。在FGF4和PD03处理下，PrE细胞和Epi细胞的多能性和再生能力（Credit: Cell）实验处理和设计：通过将8细胞阶段的小鼠胚胎分别用成纤维细胞生长因子4（FGF4）和MEK抑制剂PD0329501（PD03）处理24小时，将其分别转化为原始内胚层（primitive endoderm, PrE）或胚胎上皮细胞（epiblast, Epi）。处理后，通过免疫手术去除外胚层（trophectoderm, TE），并在不同条件下培养这些胚胎。 PrE的多能性和再生能力：在去除TE后，单独的PrE细胞能够再生出完整的囊胚。这些再生出的囊胚包含了TE、Epi和PrE细胞。经过FGF4处理的胚胎中，76.9%的胚胎完全表达GATA6，而没有NANOG表达。这表明这些胚胎转化为PrE。再生后的胚胎在恢复48小时后，有79.2%的对照胚胎和63.6%的FGF4处理胚胎能够重建TE。在PD03处理的胚胎中，81.2%的胚胎完全表达NANOG，没有GATA6表达。这表明这些胚胎转化为Epi。然而，只有29%的PD03处理胚胎能够重建TE。细胞命运追踪：使用转基因小鼠模型，通过Cre-loxP系统特异性标记和追踪PrE细胞，发现PrE细胞能够再生TE和Epi细胞。在这些实验中，重新构建的囊胚中，CDX2和NANOG与mGFP共表达，表明先前表达PDGFRA的PrE细胞转换为Epi或TE细胞。细胞命运决定的实验验证：在进一步的实验中，通过在体外条件下释放FGF4刺激，PrE细胞能够在完整TE的背景下生成Epi细胞。大多数（89%）胚胎在处理后包含NANOG阳性细胞，表明PrE细胞具有生成Epi的能力。使用Pdgfra-CreERT2和Rosa26mT/mG小鼠模型，经过FGF4处理和4OHT诱导后，E4.5阶段的胚胎中包含NANOG和mGFP共表达细胞，进一步确认了PrE细胞的多能性。功能性验证：将成功重建的FGF4处理和对照胚胎移植到假孕小鼠中，发现重新构建的胚胎能够支持正常发育，表达Epi、VE/PE和胚外外胚层（extra-embryonic ectoderm）的标记物。 PrE细胞的多能性 PrE再生囊胚：研究发现，在去除TE后，单独的PrE细胞能够再生出完整的囊胚。经过FGF4处理的胚胎中，76.9%的胚胎完全表达GATA6，而没有NANOG表达，这表明这些胚胎转化为PrE。再生TE和Epi：经过进一步培养，这些PrE胚胎能够再生出TE和Epi细胞，表明PrE细胞具有强大的多能性。在移植实验中，PrE细胞能够形成正常发育的胚胎，进一步验证了其多能性。增强子景观的调控 OCT4维持多能性：在体外培养的nEnd细胞中，OCT4的持续表达维持了细胞的多能性。使用带有OCT4-mCherry报告基因的细胞系，通过流式细胞术分选出PDGFRA-APC阳性细胞、双阳性细胞（PDGFRA-APC/OCT4-mCherry）和OCT4-mCherry单阳性细胞，观察到双阳性细胞能够生成TE和Epi样细胞。 JAK/STAT信号通路：通过阻断JAK/STAT信号通路，发现去除该信号会导致多能性细胞减少，而单阳性细胞比例增加，表明JAK/STAT信号在维持多能性过程中起关键作用。体外模型验证 nEnd细胞形成3D球体：在三维培养条件下，nEnd细胞能够自发形成具有内外层结构的球体，外层为GATA6阳性细胞，内层为SOX2阳性细胞，模拟了胚胎早期的分化状态。这些球体的形成效率高达61.3%。模式图（Credit: Cell）原始内胚层（PrE）在哺乳动物胚胎发育中的多能性和调控能力为我们提供了一个理解细胞命运决定和发育调控的独特模型。通过对PrE细胞的研究，研究人员不仅揭示了其在胚胎发育中的关键作用，还为再生医学和发育生物学的研究提供了新的方向和思路。未来的研究可以进一步探讨PrE细胞在不同生理和病理条件下的行为，以及如何利用这些细胞进行疾病治疗和再生医学应用。这一研究不仅挑战了传统观点，即PrE只是简单的支持组织，还表明它在胚胎发育的调控性过程中发挥了重要作用。通过深入研究PrE的分子基础和其在多能性维持中的作用，可以更好地理解胚胎发育的复杂性及其潜在的应用前景。参考文献 Linneberg-Agerholm M, Sell AC, Redó-Riveiro A, Perera M, Proks M, Knudsen TE, Barral A, Manzanares M, Brickman JM. The primitive endoderm supports lineage plasticity to enable regulative development. Cell. 2024 Jun 20:S0092-8674(24)00595-6. doi: 10.1016/j.cell.2024.05.051. Epub ahead of print. PMID: 38917790. https://doi.org/10.1016/j.cell.2024.05.051 责编|探索君排版|探索君转载请注明来源于【生物探索】 End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell 综述

细胞疗法

2024-06-11

·BioSpace

The Novartis Oncology Young Canadian Investigator Awards (NOYCIA) returns for its 21st year at ASCO 2024

NOYCIA recognizes excellence in Canadian oncology research as part of Novartis Canada's commitment to reimagining medicine MONTREAL, June 11, 2024 /CNW/ - Novartis Canada is pleased to announce the winners of the 2024 Novartis Oncology Young Canadian Investigator Awards (NOYCIA), an annual national competition dedicated to advancing oncology through the promotion of research by supporting Canadian oncology researchers. This year marks the 21st year of the awards which took place on Sunday, June 2nd at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. Each year, NOYCIA celebrates the innovative work of ten Canadian researchers who have had their abstracts accepted at ASCO and demonstrate excellence in their area of study. Following extensive and objective deliberation by a dedicated Scientific Panel, ten Canadian oncology researchers were selected based on the merit of their research to be the 2024 winners and receive a grant to support their ongoing work. "At Novartis, we harness the innovation of our world-class scientists, strategic partnerships, and one of the industry's most competitive pipelines to make the promise of next-generation medicines a reality," said Sophia Kajla, Chief Scientific Officer and Vice-President, Medical Affairs, Novartis Canada. "Since NOYCIA's inaugural year in 2004, winners have gone on to become medical experts and pay it forward by sharing their talent to help nurture and grow the next generation of emerging Canadian leaders in oncology." The NOYCIA 2024 recipients are: Arkhjamil Angeles, Resident, B.C. Cancer Agency: Delayed immune-related adverse events in patients with advanced melanoma treated with immune checkpoint inhibitors Matthew Dankner, Resident, McGill University: Cold-inducible RNA-binding protein is a context-specific functional mediator of breast cancer metastasis Mitchell Elliott, Resident, Princess Margaret Cancer Centre: Evaluating metrics of circulating tumor DNA response and progression using a high sensitivity tumor-agnostic assay in metastatic HR+/HER2- breast cancer receiving endocrine therapy and a CDK4/6-inhibitor Mercedes Herrera, Fellow, Princess Margaret Cancer Centre: Endogenous retrotransposable elements as a novel predictive biomarker of response to immunotherapy Sameena Khan, Fellow, Princess Margaret Cancer Centre: ctDNA Lung DETECT Ronan McLaughlin, Fellow, Princess Margaret Cancer Centre: GATA6 expression in advanced pancreatic ductal adenocarcinoma (PDAC) as a prognostic and predictive biomarker in the Canadian COMPASS trial and the Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS Erick Saldanha, Post Doctoral Fellow, Princess Margaret Cancer Centre: Circulating metabolic profiling as a biomarker for immune checkpoint blockade efficacy Xin (Kevin) Wang, Fellow, Princess Margaret Cancer Centre: A phase II trial of olaparib and durvalumab in patients with recurrent IDH-mutated gliomas Matt Warkentin, Post Doctoral Associate, University of Calgary: Risk of developing a subsequent primary cancer among adult cancer survivors Martin Zarba, Fellow, University of Calgary: Systemic treatments in favorable and very favorable risk metastatic renal cell carcinoma (mRCC): Real world evidence from the international mRCC Database Consortium (IMDC) "I am honoured to serve as the Chair on this Scientific Panel, dedicated to recognizing the expertise of emerging oncology researchers in Canadian institutions," said Dr. Paul Wheatley-Price, NOYCIA Chair and medical oncologist, The Ottawa Hospital. "For over two decades, NOYCIA has been, and continues to be, outstanding in propelling oncology forward through the endorsement of research, and it's deeply rewarding to be part of such a terrific initiative." NOYCIA's 2024 itinerary includes the Mentorship Matters Program which offers mentorship opportunities to trainees who attend the NOYCIA awards dinner. The program provides trainees with the opportunity to network with key figures at Canadian cancer centres. Canadian oncology colleagues co-host a table during the NOYCIA awards dinner and trainees from across Canada have the opportunity to hear from mentors about career paths, programs and opportunities that their centres provide and to ask questions. Mentors have the opportunity to pay it forward by sharing their career and research wisdom to the future generation of medical oncologists, to inspire and meet candidates seeking employment and to have fun. About the Novartis Oncology Young Investigators Award (NOYCIA) With a mission to support Canadian oncology researchers, NOYCIA provides funding, support, and recognition to 10 researchers that demonstrate excellence in their specialist field of study. Eligible applicants include Post-Doctorate Students, Residents, Fellows, Graduate Students, Medical Students, PhD Candidates and Undergraduates who are affiliated with a Canadian institution and are the first author of an abstract accepted for the annual ASCO meeting. For more information about NOYCIA, please visit . About Novartis Novartis is a focused innovative medicines company. Every day, we work to reimagine medicine to improve and extend people's lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. Reimagine medicine with us: Visit us at and connect with us on LinkedIn, Facebook, X/Twitter and Instagram. In Canada, Novartis Pharmaceuticals Canada Inc. employs approximately 600 people to serve the evolving needs of patients and the healthcare system and invests over $30 million in R&D yearly in the country. For more information visit . 451380E SOURCE Novartis Pharmaceuticals Canada Inc.

临床2期免疫疗法ASCO会议

2023-12-23

·生物制药小编

TRM-TAM来源与分化的差异性：人vs小鼠

组织驻留巨噬细胞(TRM)在免疫和组织修复中具有独特的转录特征和功能，同时也是小鼠和人体肿瘤相关巨噬细胞(TAM)的重要来源。然而人和小鼠中的巨噬细胞分子生物学描述并不相同。TRM异质性对TAM的影响在肺癌、胰腺癌和乳腺癌的小鼠模型中，组织驻留巨噬细胞来源的肿瘤相关巨噬细胞(TRM-TAMs)积极支持早期肿瘤扩散并促进肿瘤生长。TRM-TAM在不同的癌症中表现出不同的功能特性。例如，胰腺中的TRM-TAM表现出独特的促纤维化表型，产生和重塑细胞外基质分子；肺TRM-TAM则通过诱导肿瘤细胞上皮-间充质转化和突出的Treg细胞诱导来减弱抗肿瘤适应性免疫反应，从而促进肿瘤侵袭；TIM4+胸/腹膜腔驻留巨噬细胞通过将CD8+ T细胞隔离在远离肿瘤靶点的部位上来损害抗肿瘤免疫。一组可自我更新的CD163+ TIM4+ 组织驻留网膜巨噬细胞通过为肿瘤干细胞提供保护性生态位，与卵巢癌细胞的转移扩散有因果关系，等等。而在TAMs研究中发现，TAM的不同来源(比如TRM来源和单核细胞来源)可能导致其对耗竭或调节干预表现出不同的敏感性，在治疗中或许就需要双重TAM靶向策略以提高免疫治疗效果。同时，人和小鼠中不同表征的巨噬细胞分化阶段的比例在两个物种之间有很大的差异，也会影响对于临床疗效的判断。cavity macrophages：人vs鼠组织驻留的网膜腔巨噬细胞是TAM的重要来源之一，在卵巢癌、肝纤维化等实体瘤TME的形成中起到重要作用。大多数小鼠网膜巨噬细胞特征是GATA6+和CXCL1、SELP等其他相关基因的表达。体内动态平衡中，小鼠腹膜巨噬细胞存在两种不同的巨噬细胞群。（一）大腹腔巨噬细胞(LCM)LCM是更主要的巨噬细胞群，仅存在于腹膜、胸膜和心包腔的腔液中。表征：LCM表达F4/80hi CD115+ ICAM2+，来源于胚胎前体，依赖转录因子GATA6进行发育和维持。在没有GATA6的情况下，LCM会下调CD73，并上调CD206和LYVE1等。功能：作为对炎症或损伤的反应，LCM通过聚集在扰动的空洞表面或纤维蛋白凝块内来帮助遏制早期感染发生。（二）小腹腔巨噬细胞(SCM)表征：SCM表达F4/80lo MHCII+，超过75%的SCM还表达CD226。该亚群起源于类似于单核细胞的CCR2依赖性前体，其发育程序依赖于转录因子IRF4。功能：以前一般将其归类为M1类巨噬细胞。但是其中部分群体的同时表达巨噬细胞和DC的混合功能特征。LCM和SCM都表达CD115和和CD11b。在人体中：尽管人体中同样存在GATA6+的腹膜巨噬细胞，但是数量非常少。相对地，人体中数量丰富的CCR2+或GLUL+巨噬细胞则没有在小鼠中发现明显对应的亚群。CCR2+也代表了与单核细胞浸润有关的早期分化阶段。若要对应，人体表达GATA6+的巨噬细胞亚群为TIMD4+亚群，和小鼠中的GATA6+ LCM1亚群一样表达SELP信使RNA。而表达相同RNA的其他巨噬细胞还包括：MRC1+ LYVE1+ CD163+ 巨噬细胞；GLUL+ CD163++ FABP5+ 巨噬细胞；Marco+ 巨噬细胞；IL1B+ 巨噬细胞；干扰素刺激基因(ISG)+ 巨噬细胞；CCR2+ 巨噬细胞；以及CD1C+CD14+ 巨噬细胞。其中，小鼠中存在和MRC1+LYVE1+CD163+ 巨噬细胞同样表达和起源的亚群，但是比例比人体内更少。这代表着人腹腔巨噬细胞的分化周期相对于小鼠来说，更多存在于GATA6表达之前的分化阶段，许多巨噬细胞似乎在GATA6表达之前的阶段停滞或在表达后不久死亡。而CD1C+CD14+ 巨噬细胞则和小鼠F4/80lo MHCII+ SCM具有相似的特征。人CD1C+ 细胞在小鼠中可对应CD226+ 干细胞。在人体中，CD1C+细胞相对丰富，可分为：CD1C+ CD14+亚群：表达编码CD16、CD115、CD63、CD163和巨噬细胞相关基因；CD1C+ CD14- 亚群：表达一些DC经典表征基因，包括LTB、肥大细胞特异性表征FCER1A、CD37和CD1E。同时，CD1c+人腹膜单核巨噬细胞群中同样存在具有混合巨噬细胞和DC特征的CD1c+ cDC2和CD1c+ CD14+ CD64+ CD226+ 细胞亚群。小结巨噬细胞的亚群表征多样，在人体中的研究也尚待继续完善。F4/80、Ly6G和Ly6C等小鼠特异性分子标记物在人巨噬细胞中不表达，为研究中在小鼠模型和人体之间进行翻译带来了困难。更准确的亚群特征对应研究或提高TME相关免疫疗法的可行性。参考文献：1.Han, J., Gallerand, A., Erlich, E.C. et al. Human serous cavity macrophages and dendritic cells possess counterparts in the mouse with a distinct distribution between species. Nat Immunol (2023). https://doi.org/10.1038/s41590-023-01688-72.Andrea Vogel, Thomas Weichhart,Tissue-resident macrophages — early passengers or drivers in the tumor niche?,Current Opinion in Biotechnology,Volume 83,2023,102984,ISSN 0958-1669,https://doi.org/10.1016/j.copbio.2023.102984.3.Zhi Wang, Kailei Du, Nake Jin, Biao Tang, Wenwu Zhang,Macrophage in liver Fibrosis: Identities and mechanisms,International Immunopharmacology,Volume 120,2023,110357,ISSN 1567-5769,https://doi.org/10.1016/j.intimp.2023.110357.

免疫疗法