Evidence map›Paper›PMID 31238970›Full record

ArticleJournal for immunotherapy of cancer2019

Optimized fractionated radiotherapy with anti-PD-L1 and anti-TIGIT: a promising new combination.

Mathieu Grapin, Corentin Richard, Emeric Limagne, Romain Boidot, Véronique Morgand, Aurélie Bertaut, Valentin Derangere, Pierre-Antoine Laurent, Marion Thibaudin, Jean David Fumet and 3 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed, 4 pooled it
9.8field-weighted citation impact, top 1% 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

131 citing papers in PubMed, 4 syntheses or guidelines pooled it, 208 citations in OpenAlex.

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71 more citing papers are in PubMed but not listed here.

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 2 institutions in 2 countries.

Mathieu GrapinDepartment of Radiation Oncology, Unicancer - Georges-Francois Leclerc Cancer Center, 1 rue Professeur Marion 77 980, 21079, Dijon Cedex, BP, France.
Corentin RichardCancer Biology Research Platform, Unicancer - Georges-Francois Leclerc Cancer Center, Dijon, France.
Emeric LimagneCancer Biology Research Platform, Unicancer - Georges-Francois Leclerc Cancer Center, Dijon, France.
Romain BoidotCancer Biology Research Platform, Unicancer - Georges-Francois Leclerc Cancer Center, Dijon, France.
Véronique MorgandDepartment of Radiation Oncology, Unicancer - Georges-Francois Leclerc Cancer Center, 1 rue Professeur Marion 77 980, 21079, Dijon Cedex, BP, France.
Aurélie BertautMethodology, data-management and biostatistics unit, Unicancer - Georges-Francois Leclerc Cancer Center , Dijon, France.
Valentin DerangereCancer Biology Research Platform, Unicancer - Georges-Francois Leclerc Cancer Center, Dijon, France.
Pierre-Antoine LaurentDepartment of Radiation Oncology, Unicancer - Georges-Francois Leclerc Cancer Center, 1 rue Professeur Marion 77 980, 21079, Dijon Cedex, BP, France.
Marion ThibaudinCancer Biology Research Platform, Unicancer - Georges-Francois Leclerc Cancer Center, Dijon, France.
Jean David FumetCancer Biology Research Platform, Unicancer - Georges-Francois Leclerc Cancer Center, Dijon, France.
Gilles CrehangeDepartment of Radiation Oncology, Unicancer - Georges-Francois Leclerc Cancer Center, 1 rue Professeur Marion 77 980, 21079, Dijon Cedex, BP, France.
François GhiringhelliCancer Biology Research Platform, Unicancer - Georges-Francois Leclerc Cancer Center, Dijon, France.
Céline MirjoletDepartment of Radiation Oncology, Unicancer - Georges-Francois Leclerc Cancer Center, 1 rue Professeur Marion 77 980, 21079, Dijon Cedex, BP, France. cmirjolet@cgfl.fr.ORCID 0000-0003-0047-9421
Centre Georges François Leclerc · FRInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

PURPOSE/

objectiveRadiotherapy (RT) induces an immunogenic antitumor response, but also some immunosuppressive barriers. It remains unclear how different fractionation protocols can modulate the immune microenvironment. Clinical studies are ongoing to evaluate immune checkpoint inhibitors (ICI) in association with RT. However, only few trials aim to optimize the RT fractionation to improve efficacy of these associations. Here we sought to characterize the effect of different fractionation protocols on immune response with a view to associating them with ICI. MATERIALS/

methodsMice bearing subcutaneous CT26 colon tumors were irradiated using a SARRP device according to different radiation schemes with a same biologically effective dose. Mice were monitored for tumor growth. The radiation immune response (lymphoid, myeloid cells, lymphoid cytokines and immune checkpoint targets) was monitored by flow cytometry at different timepoints after treatment and by RNA sequencing analysis (RNAseq). The same radiation protocols were performed with and without inhibitors of immune checkpoints modulated by RT.

resultsIn the absence of ICI, we showed that 18x2Gy and 3x8Gy induced the longest tumor growth delay compared to 1×16.4Gy. While 3x8Gy and 1×16.4Gy induced a lymphoid response (CD8

conclusionEach fractionation scheme induced different lymphoid and myeloid responses as well as various modulations of PD-L1 and TIGIT expression. Furthermore, 3x8Gy was the most effective protocol when associated with anti-PD-L1 and anti-TIGIT. This is the first study combining RT and anti-TIGIT with promising results; further studies are warranted.

Indexed as

AnimalsAntineoplastic Agents, ImmunologicalB7-H1 AntigenCell Line, TumorColonic NeoplasmsCombined Modality TherapyDose Fractionation, RadiationFemaleMice, Inbred BALB CMice, Inbred C57BLMice, NudeReceptors, ImmunologicAntineoplastic Agents, ImmunologicalB7-H1 AntigenCD274 protein, humanReceptors, ImmunologicTIGIT protein, humanColorectal cancerImmune responseImmunotherapyRadiotherapy fractionation

Identifiers

PMID31238970
PMCPMC6593525
OpenAlexW2954764274

What OpenQuestion holds

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Registered trials

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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.