ArticleCancer immunology, immunotherapy : CII2021
Combined vaccine-immune-checkpoint inhibition constitutes a promising strategy for treatment of dMMR tumors.
Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Pro-tumourigenic effects of DCAF13 on the progression of colorectal cancer.Oncology letters · 2026Article
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- CircRNAs in Colorectal Cancer: Unveiling Their Roles and Exploring Therapeutic Potential.Biochemical genetics · 2025Review
- Nanoformulations Downregulating METTL16 Combined with mRNA Tumor Vaccines Suppress Triple-Negative Breast Cancer and Prevent Metastasis.International journal of nanomedicine · 2025Article
- Advances in Tumor Antigen Vaccines: A New Frontier in Cancer Immunotherapy.International journal of medical sciences · 2025Review
- Prophylaxis with abemaciclib delays tumorigenesis in dMMR mice by altering immune responses and reducing immunosuppressive extracellular vesicle secretion.Translational oncology · 2024Article
- Short-term immune-checkpoint inhibition partially rescues perturbed bone marrow hematopoiesis in mismatch-repair deficient tumors.Oncoimmunology · 2023Article
- CDK4/6 blockade provides an alternative approach for treatment of mismatch-repair deficient tumors.Oncoimmunology · 2022Article
- The effects of dendritic cell-based vaccines in the tumor microenvironment: Impact on myeloid-derived suppressor cells.Frontiers in immunology · 2022Review
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8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMlh1-knock-out-driven mismatch-repair-deficient (dMMR) tumors can be targeted immunologically. By applying therapeutic tumor vaccination, tumor growth is delayed but escape mechanisms evolve, including upregulation of immune-checkpoint molecules (LAG-3, PD-L1). To counteract immune escape, we investigated the therapeutic activity of a combined tumor vaccine-immune-checkpoint inhibitor therapy using α-PD-L1.
designIn this trial, Mlh1-knock-out mice with established gastrointestinal tumors received single or thrice injections of α-PD-L1 monoclonal antibody clone 6E11 (2.5 mg/kg bw, q2w, i.v.) either alone or in combination with the vaccine. Longitudinal flow cytometry and PET/CT imaging studies were followed by ex vivo functional immunological and gene expression assays.
results6E11 monotherapy slightly increased median overall survival (mOS: 6.0 weeks vs. control 4.0 weeks). Increasing the number of injections (n = 3) improved therapy outcome (mOS: 9.2 weeks) and was significantly boosted by combining 6E11 with the vaccine (mOS: 19.4 weeks vs. 10.2 weeks vaccine monotherapy). Accompanying PET/CT imaging confirmed treatment-induced tumor growth control, with the strongest inhibition in the combination group. Three mice (30%) achieved a complete remission and showed long-term survival. Decreased levels of circulating splenic and intratumoral myeloid-derived suppressor cells (MDSC) and decreased numbers of immune-checkpoint-expressing splenic T cells (LAG-3, CTLA-4) accompanied therapeutic effects. Gene expression and protein analysis of residual tumors revealed downregulation of PI3K/Akt/Wnt-and TGF-signaling, leading to T cell infiltration, reduced numbers of macrophages, neutrophils and MDSC.
conclusionsBy successful uncoupling of the PD-1/PD-L1 axis, we provide further evidence for the safe and successful application of immunotherapies to combat dMMR-driven malignancies that warrants further investigation.
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