Evidence map›Paper›PMID 21515097›Full record

ArticleMolecular oncology2011

Reversal of gastrointestinal carcinoma-induced immunosuppression and induction of antitumoural immunity by a combination of cyclophosphamide and gene transfer of IL-12.

Mariana Malvicini, Mariana Ingolotti, Flavia Piccioni, Mariana Garcia, Juan Bayo, Catalina Atorrasagasti, Laura Alaniz, Jorge B Aquino, Jaime A Espinoza, Manuel Gidekel and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
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  14. New insights into IL-12-mediated tumor suppression.Cell death and differentiation · 2015
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  20. IL-12 based gene therapy in veterinary medicine.Journal of translational medicine · 2012
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Mariana MalviciniGene Therapy Laboratory, Liver Unit, School of Medicine, Austral University, Derqui-Pilar, Buenos Aires, Argentina.
Mariana Ingolotti
Flavia Piccioni
Mariana Garcia
Juan Bayo
Catalina Atorrasagasti
Laura Alaniz
Jorge B Aquino
Jaime A Espinoza
Manuel Gidekel
O Graciela Scharovsky
Pablo Matar
Guillermo Mazzolini
Austral University · ARNational University of Rosario · ARAdolfo Ibáñez University · CLUniversidad de La Frontera · CL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immunotherapy-based strategies for gastrointestinal carcinomas (GIC) have been exploited so far, but these approaches have to face strong mechanisms of immune escape induced by tumours. We previously demonstrated that sub-therapeutic doses of an adenovirus expressing IL-12 genes (AdIL-12) mediated a potent antitumour effect against subcutaneous (s.c.) colorectal carcinomas (CRC) in mice pre-treated with low doses of cyclophosphamide (Cy). In our study we used this combination to assess its impact on the immunosuppressive microenvironment. In s.c. CRC model we demonstrated that non-responder mice failed to decrease Tregs in tumour, spleen and peripheral blood. Reconstitution of Tregs into tumour-bearing mice treated with combined therapy abolished the antitumoural effect. In addition, Cy + AdIL-12 modified Tregs functionality by inhibiting the in vitro secretion of IL-10 and TGF-β and their ability to inhibit dendritic cells activation. Combined treatment decreased the number of myeloid-derived suppressor cells (MDSCs) in comparison to non-treated mice and, interestingly, administration of Tregs restored splenic MDSCs population. Furthermore, combined therapy potently generated specific cytotoxic IFN-γ-secreting CD4+ T cells able to eradicate established CRC tumours after adoptive transfer. Finally, we evaluated the combination on disseminated CRC and pancreatic carcinoma (PC). Cy + AdIL-12 were able to eradicate liver metastatic CRC (47%) and PC tumour nodules (40%) and to prolong animal survival. The results of this study support the hypothesis that Cy + AdIL-12 might be a valid immunotherapeutic strategy for advanced GIC.

Indexed as

Immunosuppression TherapyAdenoviridaeAdoptive TransferAnimalsAntineoplastic AgentsCombined Modality TherapyCyclophosphamideDendritic CellsDisease Models, AnimalGastrointestinal NeoplasmsGene Transfer TechniquesHumansImmunityInterferon-gammaInterleukin-10Interleukin-12Antineoplastic AgentsCyclophosphamideInterferon-gammaInterleukin-10Interleukin-12Transforming Growth Factor beta

Identifiers

PMID21515097
PMCPMC5528288
OpenAlexW1992727359

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.