{rfName}
LA

Indexed in

License and use

Citations

525

Altmetrics

Grant support

This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (Milan, Italy) and the European Community (Cancer Immunotherapy, Contract No. 518234).

Analysis of institutional authors

Castelletti, ChiaraAuthor

Share

April 10, 2020
Publications
>
Article
No

LAG-3 Expression Defines a Subset of CD4(+)CD25(high)Foxp3(+) Regulatory T Cells That Are Expanded at Tumor Sites

Publicated to:JOURNAL OF IMMUNOLOGY. 184 (11): 6545-6551 - 2010-06-01 184(11), DOI: 10.4049/jimmunol.0903879

Authors: Camisaschi, Chiara; Casati, Chiara; Rini, Francesca; Perego, Michela; De Filippo, Annamaria; Rini, Frederic; Parmiani, Giorgio; Belli, Filiberto; Rivoltini, Licia; Castelli, Chiara;

Affiliations

Immutep SA, Fac Pharm, Chatenay Malabry, France - Author
Ist Nazl Tumori, Unit Colorectal Surg, Fdn Ist Ricovero & Cura Carattere Sci, I-20133 Milan, Italy - Author
Ist Nazl Tumori, Unit Immunotherapy Human Tumors, Fdn Ist Ricovero & Cura Carattere Sci, I-20133 Milan, Italy - Author

Abstract

Human natural regulatory CD4(+) T cells comprise 5-10% of peripheral CD4(+) T cells. They constitutively express the IL-2R alpha-chain (CD25) and the nuclear transcription Foxp3. These cells are heterogeneous and contain discrete subsets with distinct phenotypes and functions. Studies in mice report that LAG-3 has a complex role in T cell homeostasis and is expressed in CD4(+)CD25(+) T regulatory cells. In this study, we explored the expression of LAG-3 in human CD4(+) T cells and found that LAG-3 identifies a discrete subset of CD4(+)CD25(high)Foxp3(+) T cells. This CD4(+)CD25(high)Foxp3(+)LAG-3(+) population is preferentially expanded in the PBMCs of patients with cancer, in lymphocytes of tumor-invaded lymph nodes and in lymphocytes infiltrating visceral metastasis. Ex vivo analysis showed that CD4(+)CD25(high)Foxp3(+)LAG-3(+) T cells are functionally active cells that release the immunosuppressive cytokines IL-10 and TGF-beta 1, but not IL-2. An in vitro suppression assay using CD4(+)CD25(high)Foxp3(+)LAG-3(+) T cells sorted from in vitro expanded CD4(+)CD25(high) high regulatory T cells showed that this subset of cells is endowed with potent suppressor activity that requires cell-to-cell contact. Our data show that LAG-3 defines an active CD4(+)CD25(high)Foxp3(+) regulatory T cell subset whose frequency is enhanced in the PBMCs of patients with cancer and is expanded at tumor sites. The Journal of Immunology, 2010, 184: 6545-6551.

Keywords

Cancer-patientsCd8(+)Effector functionFoxp3HumansIn-vivoInterleukin-10Mediates suppressionMemoryPeripheral-blood

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal JOURNAL OF IMMUNOLOGY 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, 2010, it was in position 20/134, thus managing to position itself as a Q1 (Primer Cuartil), in the category Immunology.

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: 40.16, 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 2025-07-16, the following number of citations:

  • WoS: 231
  • Scopus: 253

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 2025-07-16:

  • 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: 228.
  • 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: 232 (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: 9.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: France; Italy.