{rfName}
Ce

Indexed in

License and use

Citations

4

Altmetrics

Grant support

This study was undertaken with the support of ISCIII, Immune4all (PMP22/00054); Fundacion Asociacion Espanola contra el Cancer (AECC); ISCIII, FIS (PI22/00130); BBVA (CAIMI); and Cellex Foundation.

Impact on the Sustainable Development Goals (SDGs)

Analysis of institutional authors

Planas-Rigol, EsterAuthor

Share

October 26, 2024
Publications
>
Article
No

Cervical Cancer Evades the Host Immune System through the Inhibition of Type I Interferon and CXCL9 by LIF

Publicated to:Clinical Cancer Research. 30 (19): 4505-4516 - 2024-10-01 30(19), DOI: 10.1158/1078-0432.CCR-24-0385

Authors: Bonfill-Teixidor, Ester; Neva-Alejo, Almudena; Arias, Alexandra; Cuartas, Isabel; Iurlaro, Raffaella; Planas-Rigol, Ester; Sole, Laura; Pecharroman, Irene; Cabrera, Silvia; Garcia, Angel; Garcia-Illescas, David; Espinosa, Lluis; Gil-Moreno, Antonio; Oaknin, Ana; Seoane, Joan

Affiliations

Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain - Author
Hosp Del Mar, Inst Mar Invest Med, Canc Res Program, CIBERONC, Barcelona, Spain - Author
Institucio Catalana Recerca & Estudis Avancats ICR, Barcelona, Spain - Author
Univ Autonoma Barcelona UAB, Cerdanyola Del Valles, Spain - Author
Vall dHebron Univ Hosp, Vall dHebron Inst Oncol VHIO, Barcelona, Spain - Author
Vall Hebron Univ Hosp, Pathol Dept, Barcelona, Spain - Author
Vall Hebron Univ Hosp, Vall Hebron Res Inst VHIR, Gynecol Dept, Barcelona, Spain - Author
See more

Abstract

Purpose: Cervical cancer is a viral-associated tumor caused by the infection with the human papilloma virus. Cervical cancer is an immunogenic cancer that expresses viral antigens. Despite being immunogenic, cervical cancer does not fully respond to immune checkpoint inhibitors (ICI). LIF is a crucial cytokine in embryo implantation, involved in maternal tolerance that acts as an immunomodulatory factor in cancer. LIF is expressed in cervical cancer and high levels of LIF is associated with poor prognosis in cervical cancer.Experimental Design: We evaluated the impact of LIF on the immune response to ICI using primary plasmocytoid dendritic cells (pDC) and macrophage cultures, syngeneic animals and patient-derived models that recapitulate the human tumor microenvironment.Results: We found that the viral proteins E6 and E7 induce the expression of LIF via the NF kappa B pathway. The secreted LIF can then repress type I interferon expressed in pDCs and CXCL9 expressed in tumor-associated macrophages. Blockade of LIF promotes the induction of type I interferon and CXCL9 inducing the tumor infiltration of CD8 T cells. This results in the sensitization of the tumor to ICI. Importantly, we observed that patients with cervical cancer expressing high levels of LIF tend to be resistant to ICI.Conclusions: Our data show that the HPV virus induces the expression of LIF to provide a selective advantage to the tumor cell by generating local immunosuppression via the repression of type I interferon and CXCL9. Combinatory treatment with blocking antibodies against LIF and ICI could be effective against cervical cancer expressing high levels of LIF.

Keywords

Good health and well-being

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Clinical Cancer Research 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, 2024 there are still no calculated indicators, but in 2023, it was in position 29/326, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-08-12:

  • Open Alex: 1
  • WoS: 1

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 2025-08-12:

  • 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: 10.
  • 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: 8 (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: 0.75.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).
Continuing with the social impact of the work, it is important to emphasize that, due to its content, it can be assigned to the area of interest of ODS 3 - Good Health And Well-being, with a probability of 73% according to the mBERT algorithm developed by Aurora University.