ArticleCancer immunology, immunotherapy : CII2018
Chemotherapy-induced apoptosis, autophagy and cell cycle arrest are key drivers of synergy in chemo-immunotherapy of epithelial ovarian cancer.
Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Phase II study of durvalumab and tremelimumab with front-line neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer: primary analysis in the original cohort of KGOG3046/TRU-D.Journal for immunotherapy of cancer · 2023Trial
- Prognostic Impact of PD-L1 Expression in Ovarian Cancer: Analysis of a Real-World Cohort Treated With Primary Platinum-Based Chemotherapy.Cancer medicine · 2026Article
- Pharmacotherapy for Keloids and Hypertrophic Scars.International journal of molecular sciences · 2024Review
- Intratumoral Injection of Large Surface Area Microparticle Taxanes in Carcinomas Increases Immune Effector Cell Concentrations, Checkpoint Expression, and Synergy with Checkpoint Inhibitors: A Review of Preclinical and Clinical Studies.Oncology and therapy · 2024Review
- Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy.Biomedicines · 2023Review
- Review
- PD-1/PD-L1 and DNA Damage Response in Cancer.Cells · 2023Review
- A novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer.Journal of Zhejiang University. Science. B · 2023Article
- Tumor buster - where will the CAR-T cell therapy 'missile' go?Molecular cancer · 2022Review
- Is Autophagy Always a Barrier to Cisplatin Therapy?Biomolecules · 2022Review
- Translational Learnings in the Development of Chemo-Immunotherapy Combination to Bypass the Cold Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma.Frontiers in oncology · 2022Review
- Genetic Variation of PD-L1 Gene Affects its Expression and Is Related to Clinical Outcome in Epithelial Ovarian Cancer.Frontiers in oncology · 2022Article
- Primary central nervous system lymphomas express immunohistochemical factors of autophagy.Scientific reports · 2021Article
- Article
- Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment.International journal of molecular sciences · 2021Review
- Construction autophagy-related prognostic risk signature to facilitate survival prediction, individual treatment and biomarker excavation of epithelial ovarian cancer patients.Journal of ovarian research · 2021Article
- Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer.Frontiers in oncology · 2021Article
- Plinabulin, a Distinct Microtubule-Targeting Chemotherapy, Promotes M1-Like Macrophage Polarization and Anti-tumor Immunity.Frontiers in oncology · 2021Article
- Metabolic factors contribute to T-cell inhibition in the ovarian cancer ascites.International journal of cancer · 2020Review
- The Perfect Combination: Enhancing Patient Response to PD-1-Based Therapies in Epithelial Ovarian Cancer.Cancers · 2020Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial ovarian cancer (EOC) is the most lethal of all gynecological malignancies in the UK. Recent evidence has shown that there is potential for immunotherapies to be successful in treating this cancer. We have previously shown the effective application of combinations of traditional chemotherapy and CAR (chimeric antigen receptor) T cell immunotherapy in in vitro and in vivo models of EOC. Platinum-based chemotherapy synergizes with ErbB-targeted CAR T cells (named T4), significantly reducing tumor burden in mice. Here, we show that paclitaxel synergizes with T4 as well, and look into the mechanisms behind the effectiveness of chemo-immunotherapy in our system. Impairment of caspase activity using pan-caspase inhibitor Z-VAD reveals this chemotherapy-induced apoptotic pathway as an essential factor in driving synergy. Mannose-6-phosphate receptor-mediated autophagy and the arrest of cell cycle in G2/M are also shown to be induced by chemotherapy and significantly contributing to the synergy. Increased expression of PD-1 on T4 CAR T cells occurred when these were in culture with ovarian tumor cells; on the other hand, EOC cell lines showed increased PD-L1 expression following chemotherapy treatment. These findings provided a rationale to look into testing PD-1 blockade in combination with paclitaxel and T4 immunotherapy. Combination of these three agents in mice resulted in significant reduction of tumor burden, compared to each treatment alone. In conclusion, the mechanism driving synergy in chemo-immunotherapy of EOC is multifactorial. A deeper understanding of such process is needed to better design combination therapies and carefully stratify patients.
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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.