ArticleJournal for immunotherapy of cancer2019
Chemo-immunotherapy improves long-term survival in a preclinical model of MMR-D-related cancer.
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 8 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Immunosuppressive roles of pericytes in cancer disease: insights from a systematic review and meta-analysis.Journal of translational medicine · 2026Pooled it
- Advances in Hereditary Colorectal Cancer: How Precision Medicine Is Changing the Game.Cancers · 2025Review
- Prophylaxis with abemaciclib delays tumorigenesis in dMMR mice by altering immune responses and reducing immunosuppressive extracellular vesicle secretion.Translational oncology · 2024Article
- Combined vaccine-immune-checkpoint inhibition constitutes a promising strategy for treatment of dMMR tumors.Cancer immunology, immunotherapy : CII · 2021Article
- Combined Gemcitabine and Immune-Checkpoint Inhibition Conquers Anti-PD-L1 Resistance in Low-Immunogenic Mismatch Repair-Deficient Tumors.International journal of molecular sciences · 2021Article
- In vivo vaccination with cell line-derived whole tumor lysates: neoantigen quality, not quantity matters.Journal of translational medicine · 2020Article
- Review
- Unraveling the Heterogeneous Mutational Signature of Spontaneously Developing Tumors in MLH1Cancers · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMismatch Repair Deficiency (MMR-D)-related tumors are highly immunogenic and constitute ideal vaccination targets. In a proof-of-concept study delayed tumorigenesis and prolonged survival has been shown in a clinically-relevant mouse model for MMR-D-related diseases (=MLH1 knock out mice). To refine this approach, vaccination was combined with immune modulatory low-dose chemotherapy to polarize immune regulatory subtypes.
methodsMice (prophylactic: 8-10 weeks; therapeutic: > 36 weeks) received a single injection of cyclophosphamide (CPX, 120 mg/kg bw, i.p.) or gemcitabine (GEM, 100 mg/kg bw, i.p.) prior to vaccination (lysate of a gastrointestinal tumor allograft, 10 mg/kg bw, n = 9 mice/group). The vaccine was given repetitively (10 mg/kg bw, s.c., 4 x / once a week, followed by monthly boosts) until tumor formation or progression. Tumor growth ([
resultsProphylactic application of GEM + lysate delayed tumorigenesis compared to lysate monotherapy and CPX-pre-treatment (median time of onset: 53 vs. 47 vs. 48 weeks). 33% of mice even remained tumor-free until the experimental endpoint (= 65 weeks). This was accompanied by long-term effect on cytokine plasma levels; splenic myeloid derived suppressor cells (MDSC) as well as regulatory T cell numbers. Assessment of tumor microenvironment from GEM + lysate treated mice revealed low numbers of MDSCs, but enhanced T cell infiltration, in some cases co-expressing PD-L1. Therapeutic chemo-immunotherapy (GEM + lysate) had minor impact on overall survival (median time: 12 (GEM + lysate) vs. 11.5 (lysate) vs. 3 weeks (control)), but induced complete remission in one case. Dendritic and T cell infiltrates increased in both treatment groups. Reactive T cells specifically recognized MLH1
conclusionsCombined chemo-immunotherapy impairs tumor onset and growth likely attributable to modulation of immune responses. Depleting or 're-educating' immunosuppressive cell types, such as MDSC, may help moving a step closer to combat cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.