Abstract B068: Human pancreatic cancer single cell atlas reveals association of CXCL10 positive fibroblasts and basal subtype tumor cells

胰腺癌 癌症 癌相关成纤维细胞 病理 医学 癌症研究 地图集(解剖学) 生物 内科学 肿瘤科 癌细胞 解剖
作者
Ian Loveless,Samantha B Kempt,Yuesong Wu,Daniel J. Sålas-Escabillas,Kailee Hartway,Madison George,Yetunde Makinwa,T Stockdale,Samuel Zwernik,Kendyll Gartrelle,Rohit G Reddy,Daniel Long,Allison Wombell,Julie M Clark,Albert M. Levin,David S. Kwon,Ling Huang,Ralph Francescone,Débora Barbosa Vendramini‐Costa,Ben Z. Stanger,Adam M. Alessio,Andrew M. Waters,Yuehua Cui,Brian K. Theisen,Howard C. Crawford,Nina G. Steele
出处
期刊:Cancer Research [American Association for Cancer Research]
卷期号:84 (17_Supplement_2): B068-B068
标识
DOI:10.1158/1538-7445.pancreatic24-b068
摘要

Abstract Pancreatic ductal adenocarcinoma (PDAC) patients with tumors enriched for the basal-like molecular subtype exhibit severe resistance to standard of care treatments and have significantly worse overall survival, compared to patients with classical subtype enriched tumors. It is therefore important to develop resources that allow identification of novel targets in a statistically rigorous way to overcome therapeutic challenges. Here we compiled a single cell RNA sequencing (scRNAseq) atlas of the human pancreas with 229 individual patient samples, aggregated from raw data obtained from published studies. We mapped cell-type specific scRNAseq gene signatures in newly generated (n=12) and existing (n=13) spatial transcriptomics (ST) data from PDAC samples. Analysis of tumor cells from our scRNAseq atlas revealed nine transcriptionally distinct populations, two of which strongly align with a basal gene signature, correlating with worse overall survival in PDAC bulk RNAseq datasets. Deconvolution showed one of the basal populations identified to be the predominant tumor subtype in non- dissociated ST tissues and in vitro tumor cell and organoid PDAC lines. In bulk RNAseq datasets, we uncovered that myofibroblasts (myFb) expressing CXCL10 consistently correlated with both basal subtypes and were found near basal tumor cells using immunostaining. We also identified that besides immune cells, ductal cells also express CXCR3, the receptor for CXCL10, further suggesting a relationship between these cell types in PDAC tumor microenvironment (TME). Overall, we show that our newly built scRNAseq atlas, containing over 700,000 cells, integrated with ST data is a powerful resource, given that it corroborates numerous PDAC TME observations in the literature, with increased statistical power. Moreover, we uncovered a novel association between CXCL10+ myFb and basal tumor cells, underscoring the presence of unique spatial niches in PDAC that should be explored for the development of targeted therapies for this dismal disease. Citation Format: Ian M Loveless, Samantha B Kempt, Yuesong Wu, Daniel J Salas-Escabillas, Kailee Hartway, Madison George, Yetunde Makinwa, Thais Stockdale, Samuel D Zwernik, Kendyll Gartrelle, Rohit G Reddy, Daniel Long, Allison Wombell, Julie M Clark, Albert M Levin, David Kwon, Ling Huang, Ralph Francescone, Débora B Vendramini-Costa, Ben Stanger, Adam Alessio, Andrew M Waters, Yuehua Cui, Brian Theisen, Howard C Crawford, Nina G Steele. Human pancreatic cancer single cell atlas reveals association of CXCL10 positive fibroblasts and basal subtype tumor cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B068.

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
whs发布了新的文献求助10
1秒前
大模型应助活力的小蝴蝶采纳,获得10
1秒前
1秒前
乐乐应助persist采纳,获得30
2秒前
3秒前
Erin完成签到 ,获得积分0
5秒前
若邻发布了新的文献求助10
5秒前
欣慰若发布了新的文献求助10
5秒前
whs完成签到,获得积分10
6秒前
sansronds发布了新的文献求助10
6秒前
AA1Z发布了新的文献求助10
8秒前
Patrick完成签到,获得积分10
8秒前
8秒前
邢夏之完成签到 ,获得积分10
9秒前
辣辣发布了新的文献求助10
10秒前
灵寒完成签到 ,获得积分10
12秒前
12秒前
persist发布了新的文献求助30
14秒前
洋芋饭应助大胆的茗茗采纳,获得10
15秒前
sansronds完成签到,获得积分10
16秒前
nan完成签到,获得积分10
18秒前
19秒前
张狗蛋发布了新的文献求助10
20秒前
肖肖肖完成签到 ,获得积分10
24秒前
24秒前
yangy801017完成签到,获得积分10
25秒前
Ava应助王霖采纳,获得10
27秒前
努力发布了新的文献求助10
29秒前
dyuguo3完成签到 ,获得积分10
29秒前
敏尔完成签到,获得积分10
31秒前
AA1Z完成签到,获得积分10
32秒前
科目三应助AFF采纳,获得10
32秒前
33秒前
34秒前
Werner完成签到 ,获得积分10
36秒前
冰冰完成签到,获得积分10
36秒前
36秒前
aa发布了新的文献求助10
37秒前
lida发布了新的文献求助10
38秒前
高分求助中
【此为提示信息,请勿应助】请按要求发布求助,避免被关 20000
Technologies supporting mass customization of apparel: A pilot project 450
Mixing the elements of mass customisation 360
Периодизация спортивной тренировки. Общая теория и её практическое применение 310
the MD Anderson Surgical Oncology Manual, Seventh Edition 300
Nucleophilic substitution in azasydnone-modified dinitroanisoles 300
Political Ideologies Their Origins and Impact 13th Edition 260
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3781024
求助须知:如何正确求助?哪些是违规求助? 3326463
关于积分的说明 10227359
捐赠科研通 3041675
什么是DOI,文献DOI怎么找? 1669535
邀请新用户注册赠送积分活动 799095
科研通“疑难数据库(出版商)”最低求助积分说明 758734