Evidence map›Paper›PMID 30871626›Full record

ArticleJournal for immunotherapy of cancer2019

Cocultures of human colorectal tumor spheroids with immune cells reveal the therapeutic potential of MICA/B and NKG2A targeting for cancer treatment.

Tristan Courau, Julie Bonnereau, Justine Chicoteau, Hugo Bottois, Romain Remark, Laura Assante Miranda, Antoine Toubert, Mathieu Blery, Thomas Aparicio, Matthieu Allez and 1 more

Registry-linked trialOpen 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. It is linked to trial NCT03015038 (Etude de la réponse Immunitaire Dans l'adénocarcinome Colique), which is not on this map. Cited by 168 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed, 1 pooled it
9.9field-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.

NCT03015038 completednot on this map

Etude de la réponse Immunitaire Dans l'adénocarcinome Colique

TypeobservationalSponsorInstitut National de la Santé Et de la Recherche Médicale, FranceRan2017 to 2024Enrolled100ConditionsColon Adenocarcinoma
3 · Its place in the literature

Who cites it

168 citing papers in PubMed, 1 synthesis or guideline pooled it, 255 citations in OpenAlex.

  1. Pooled it
  2. A p53Molecular therapy. Oncology · 2026
    Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. A KRASMolecular therapy. Oncology · 2025
    Article
  18. Review
  19. Review
  20. Article

108 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

11 authors at 2 institutions in 2 countries.

Tristan CourauINSERM U1160, Institut de Recherche Saint-Louis, Saint Louis Hospital, Paris, France.
Julie BonnereauINSERM U1160, Institut de Recherche Saint-Louis, Saint Louis Hospital, Paris, France.
Justine ChicoteauINSERM U1160, Institut de Recherche Saint-Louis, Saint Louis Hospital, Paris, France.
Hugo BottoisINSERM U1160, Institut de Recherche Saint-Louis, Saint Louis Hospital, Paris, France.
Romain RemarkInnate Pharma, Marseille, France.
Laura Assante MirandaInnate Pharma, Marseille, France.
Antoine ToubertINSERM U1160, Institut de Recherche Saint-Louis, Saint Louis Hospital, Paris, France.
Mathieu BleryInnate Pharma, Marseille, France.
Thomas AparicioINSERM U1160, Institut de Recherche Saint-Louis, Saint Louis Hospital, Paris, France.
Matthieu AllezINSERM U1160, Institut de Recherche Saint-Louis, Saint Louis Hospital, Paris, France.
Lionel Le BourhisINSERM U1160, Institut de Recherche Saint-Louis, Saint Louis Hospital, Paris, France. lionel.le-bourhis@inserm.fr.ORCID 0000-0002-7524-3539
Inserm · FRInnate Pharma (France) · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImmunotherapies still fail to benefit colorectal cancer (CRC) patients. Relevant functional assays aimed at studying these failures and the efficacy of cancer immunotherapy in human are scarce. 3D tumor cultures, called tumor organoids or spheroids, represent interesting models to study cancer treatments and could help to challenge these issues.

methodsWe analyzed heterotypic cocultures of human colon tumor-derived spheroids with immune cells to assess the infiltration, activation and function of T and NK cells toward human colorectal tumors in vitro.

resultsWe showed that allogeneic T and NK cells rapidly infiltrated cell line-derived spheroids, inducing immune-mediated tumor cell apoptosis and spheroid destruction. NKG2D, a key activator of cytotoxic responses, was engaged on infiltrating cells. We thus assessed the therapeutic potential of an antibody targeting the specific ligands of NKG2D, MICA and MICB, in this system. Anti-MICA/B enhanced immune-dependent destruction of tumor spheroid by driving an increased NK cells infiltration and activation. Interestingly, tumor cells reacted to immune infiltration by upregulating HLA-E, ligand of the inhibitory receptor NKG2A expressed by CD8 and NK cells. NKG2A was increased after anti-MICA/B treatment and, accordingly, combination of anti-MICA/B and anti-NKG2A was synergistic. These observations were ultimately confirmed in a clinical relevant model of coculture between CRC patients-derived spheroids and autologous tumor-infiltrating lymphocytes.

conclusionsAltogether, we show that tumor spheroids represent a relevant tool to study tumor-lymphocyte interactions on human tissues and revealed the antitumor potential of immunomodulatory antibodies targeting MICA/B and NKG2A.

Indexed as

Antineoplastic Agents, ImmunologicalCell Line, TumorCell ProliferationCell SurvivalCoculture TechniquesColorectal NeoplasmsHistocompatibility Antigens Class IHT29 CellsHumansKiller Cells, NaturalMolecular Targeted TherapyNK Cell Lectin-Like Receptor Subfamily CSpheroids, CellularT-LymphocytesAntineoplastic Agents, ImmunologicalHistocompatibility Antigens Class IKLRC1 protein, humanMHC class I-related chain AMICB antigenNK Cell Lectin-Like Receptor Subfamily CColorectal cancerImmunotherapyMICA/BNKG2ASpheroids

Identifiers

PMID30871626
PMCPMC6417026
OpenAlexW2921233868

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.