File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Ex vivo profiling of PD-1 blockade using organotypic tumor spheroids

TitleEx vivo profiling of PD-1 blockade using organotypic tumor spheroids
Authors
Issue Date2018
Citation
Cancer Discovery, 2018, v. 8, n. 2, p. 196-215 How to Cite?
AbstractEx vivo systems that incorporate features of the tumor microenvironment and model the dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology and the development of effective combination therapies. Here, we demonstrate the ability to interrogate ex vivo response to ICB using murine-and patient-derived organotypic tumor spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse and human tumors retain autologous lymphoid and myeloid cell populations and respond to ICB in short-term three-dimensional microfluidic culture. Response and resistance to ICB was recapitulated using MDOTS derived from established immunocompetent mouse tumor models. MDOTS profiling demonstrated that TBK1/ IKKe inhibition enhanced response to PD-1 blockade, which effectively predicted tumor response in vivo. Systematic profiling of secreted cytokines in PDOTS captured key features associated with response and resistance to PD-1 blockade. Thus, MDOTS/PDOTS profiling represents a novel platform to evaluate ICB using established murine models as well as clinically relevant patient specimens. Significance: Resistance to PD-1 blockade remains a challenge for many patients, and biomarkers to guide treatment are lacking. Here, we demonstrate feasibility of ex vivo profi ling of PD-1 blockade to interrogate the tumor immune microenvironment, develop therapeutic combinations, and facilitate precision immuno-oncology efforts.
Persistent Identifierhttp://hdl.handle.net/10722/318699
ISSN
2023 Impact Factor: 29.7
2023 SCImago Journal Rankings: 7.533
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJenkins, Russell W.-
dc.contributor.authorAref, Amir R.-
dc.contributor.authorLizotte, Patrick H.-
dc.contributor.authorIvanova, Elena-
dc.contributor.authorStinson, Susanna-
dc.contributor.authorZhou, Chensheng W.-
dc.contributor.authorBowden, Michaela-
dc.contributor.authorDeng, Jiehui-
dc.contributor.authorLiu, Hongye-
dc.contributor.authorMiao, Diana-
dc.contributor.authorHe, Meng Xiao-
dc.contributor.authorWalker, William-
dc.contributor.authorZhang, Gao-
dc.contributor.authorTian, Tian-
dc.contributor.authorCheng, Chaoran-
dc.contributor.authorWei, Zhi-
dc.contributor.authorPalakurthi, Sangeetha-
dc.contributor.authorBittinger, Mark-
dc.contributor.authorVitzthum, Hans-
dc.contributor.authorKim, Jong Wook-
dc.contributor.authorMerlino, Ashley-
dc.contributor.authorQuinn, Max-
dc.contributor.authorVenkataramani, Chandrasekar-
dc.contributor.authorKaplan, Joshua A.-
dc.contributor.authorPortell, Andrew-
dc.contributor.authorGokhale, Prafulla C.-
dc.contributor.authorPhillips, Bart-
dc.contributor.authorSmart, Alicia-
dc.contributor.authorRotem, Asaf-
dc.contributor.authorJones, Robert E.-
dc.contributor.authorKeogh, Lauren-
dc.contributor.authorAnguiano, Maria-
dc.contributor.authorStapleton, Lance-
dc.contributor.authorJia, Zhiheng-
dc.contributor.authorBarzily-Rokni, Michal-
dc.contributor.authorCañadas, Israel-
dc.contributor.authorThai, Tran C.-
dc.contributor.authorHammond, Marc R.-
dc.contributor.authorVlahos, Raven-
dc.contributor.authorWang, Eric S.-
dc.contributor.authorZhang, Hua-
dc.contributor.authorLi, Shuai-
dc.contributor.authorHanna, Glenn J.-
dc.contributor.authorHuang, Wei-
dc.contributor.authorHoang, Mai P.-
dc.contributor.authorPiris, Adriano-
dc.contributor.authorEliane, Jean Pierre-
dc.contributor.authorStemmer-Rachamimov, Anat O.-
dc.contributor.authorCameron, Lisa-
dc.contributor.authorSu, Mei Ju-
dc.contributor.authorShah, Parin-
dc.contributor.authorIzar, Benjamin-
dc.contributor.authorThakuria, Manisha-
dc.contributor.authorLeBoeuf, Nicole R.-
dc.contributor.authorRabinowits, Guilherme-
dc.contributor.authorGunda, Viswanath-
dc.contributor.authorParangi, Sareh-
dc.contributor.authorCleary, James M.-
dc.contributor.authorMiller, Brian C.-
dc.contributor.authorKitajima, Shunsuke-
dc.contributor.authorThummalapalli, Rohit-
dc.contributor.authorMiao, Benchun-
dc.contributor.authorBarbie, Thanh U.-
dc.contributor.authorSivathanu, Vivek-
dc.contributor.authorWong, Joshua-
dc.contributor.authorRichards, William G.-
dc.contributor.authorBueno, Raphael-
dc.contributor.authorYoon, Charles H.-
dc.contributor.authorMiret, Juan-
dc.contributor.authorHerlyn, Meenhard-
dc.contributor.authorGarraway, Levi A.-
dc.contributor.authorVan Allen, Eliezer M.-
dc.contributor.authorFreeman, Gordon J.-
dc.contributor.authorKirschmeier, Paul T.-
dc.contributor.authorLorch, Jochen H.-
dc.contributor.authorOtt, Patrick A.-
dc.contributor.authorStephen Hodi, F.-
dc.contributor.authorFlaherty, Keith T.-
dc.contributor.authorKamm, Roger D.-
dc.contributor.authorBoland, Genevieve M.-
dc.contributor.authorWong, Kwok Kin-
dc.contributor.authorDornan, David-
dc.contributor.authorPaweletz, Cloud Peter-
dc.contributor.authorBarbie, David A.-
dc.date.accessioned2022-10-11T12:24:21Z-
dc.date.available2022-10-11T12:24:21Z-
dc.date.issued2018-
dc.identifier.citationCancer Discovery, 2018, v. 8, n. 2, p. 196-215-
dc.identifier.issn2159-8274-
dc.identifier.urihttp://hdl.handle.net/10722/318699-
dc.description.abstractEx vivo systems that incorporate features of the tumor microenvironment and model the dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology and the development of effective combination therapies. Here, we demonstrate the ability to interrogate ex vivo response to ICB using murine-and patient-derived organotypic tumor spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse and human tumors retain autologous lymphoid and myeloid cell populations and respond to ICB in short-term three-dimensional microfluidic culture. Response and resistance to ICB was recapitulated using MDOTS derived from established immunocompetent mouse tumor models. MDOTS profiling demonstrated that TBK1/ IKKe inhibition enhanced response to PD-1 blockade, which effectively predicted tumor response in vivo. Systematic profiling of secreted cytokines in PDOTS captured key features associated with response and resistance to PD-1 blockade. Thus, MDOTS/PDOTS profiling represents a novel platform to evaluate ICB using established murine models as well as clinically relevant patient specimens. Significance: Resistance to PD-1 blockade remains a challenge for many patients, and biomarkers to guide treatment are lacking. Here, we demonstrate feasibility of ex vivo profi ling of PD-1 blockade to interrogate the tumor immune microenvironment, develop therapeutic combinations, and facilitate precision immuno-oncology efforts.-
dc.languageeng-
dc.relation.ispartofCancer Discovery-
dc.titleEx vivo profiling of PD-1 blockade using organotypic tumor spheroids-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/2159-8290.CD-17-0833-
dc.identifier.pmid29101162-
dc.identifier.scopuseid_2-s2.0-85041418590-
dc.identifier.volume8-
dc.identifier.issue2-
dc.identifier.spage196-
dc.identifier.epage215-
dc.identifier.eissn2159-8290-
dc.identifier.isiWOS:000424774500025-
dc.identifier.f1000732073411-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats