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Analysis of institutional authors

Rodriguez Garcia, AlbaAuthor

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June 21, 2020
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Multiparameter comparative analysis reveals differential impacts of various cytokines on CART cell phenotype and function ex vivo and in vivo

Publicated to:Oncotarget. 7 (50): 82354-82368 - 2016-12-13 7(50), DOI: 10.18632/oncotarget.10510

Authors: Xu, Xiao-Jun; Song, De-Gang; Poussin, Mathilde; Ye, Qunrui; Sharma, Prannda; Rodriguez-Garcia, Alba; Tang, Yong-Min; Powell, Daniel J

Affiliations

Penn Medicine - Author
The Children's Hospital Zhejiang University School of Medicine - Author
Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA - Author
Univ Penn, Ovarian Canc Res Ctr, Perelman Sch Med, Dept Obstet & Gynaecol, Philadelphia, PA 19104 USA - Author
University of Pennsylvania Perelman School of Medicine - Author
Zhejiang Univ, Childrens Hosp, Sch Med, Dept Hematol Oncol, Hangzhou, Zhejiang, Peoples R China - Author
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Abstract

Exogenous cytokines are widely applied to enhance the anti-tumor ability of immune cells. However, systematic comparative studies of their effects on chimeric antigen receptor (CAR)-engineered T (CART) cells are lacking. In this study, CART cells targeting folate receptor-alpha were generated and expanded ex vivo in the presence of different cytokines (IL-2, IL-7, IL-15, IL-18, and IL-21), and their expansion, phenotype and cytotoxic capacity were evaluated, in vitro and in vivo. Moreover, the effect of the administration of these cytokines along with CART cells in vivo was also studied. IL-2, IL-7, and IL-15 favored the ex vivo expansion of CART cells compared to other cytokines or no cytokine treatment. IL-7 induced the highest proportion of memory stem cell-like CART cells in the final product, and IL-21 supported the expansion of CART cells with a younger phenotype, while IL-2 induced more differentiated CART cells. IL-2 and IL-15-exposed CART cells secreted more proinflammatory cytokines and presented stronger tumor-lysis ability in vitro. However, when tested in vivo, CART cells exposed to IL-2 ex vivo showed the least anti-tumor effect. In contrast, the administration of IL-15 and IL-21 in combination with CART cells in vivo increased their tumor killing capacity. According to our results, IL-7 and IL-15 show promise to promote ex vivo expansion of CART cells, while IL- 15 and IL-21 seem better suited for in vivo administration after CART cell infusion. Collectively, these results may have a profound impact on the efficacy of CART cells in both hematologic and solid cancers.

Keywords

adoptive immunotherapychimeric antigen receptorcytokinet cellsAdoptive immunotherapyAnimalsCell line, tumorCell proliferationChimeric antigen receptorCoculture techniquesCytokineCytokinesCytotoxicity, immunologicFemaleHumansImmunotherapy, adoptiveLymphocyte activationMice, inbred nodMice, scidOvarian cancerOvarian neoplasmsPhenotypeReceptors, antigen, t-cellRecombinant fusion proteinsT cellsT-lymphocytesTime factorsTransfectionXenograft model antitumor assays

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Oncotarget due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2016, it was in position 44/217, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 5.65, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-17, the following number of citations:

  • WoS: 32
  • Scopus: 22
  • Europe PMC: 27

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-17:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 125.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 126 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 17.7.
  • The number of mentions on the social network X (formerly Twitter): 10 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: China; United States of America.