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Postablation Immune Microenvironment: Synergy between Interventional Oncology and Immuno-oncology.

ABSTRACT: Current tumor thermal ablation techniques rely on extreme temperatures to induce irreversible cellular injury and coagulative tissue necrosis. Ablation-induced cellular injury or death releases cancer neoantigens and activates the cancer-immunity cycle, potentially generating tumor-specific immune effectors. However, multiple negative regulatory modulators exist at each step of the cycle, mitigating meaningful and therapeutic anticancer effect provided by the immune system. Recent studies have focused on the introduction and testing of adjuvant immunotherapy combined with ablation to synergistically shift the equilibrium out of inhibitory immune modulation. This article reviews the immune microenvironment in relation to image-guided ablation techniques and discusses current and upcoming novel strategies to take advantage of antitumor immunity.

SUBMITTER: Kim D

PROVIDER: S-EPMC6823044 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Postablation Immune Microenvironment: Synergy between Interventional Oncology and Immuno-oncology.

Kim DaeHee D Erinjeri Joseph P JP

Seminars in interventional radiology 20191031 4

Current tumor thermal ablation techniques rely on extreme temperatures to induce irreversible cellular injury and coagulative tissue necrosis. Ablation-induced cellular injury or death releases cancer neoantigens and activates the cancer-immunity cycle, potentially generating tumor-specific immune effectors. However, multiple negative regulatory modulators exist at each step of the cycle, mitigating meaningful and therapeutic anticancer effect provided by the immune system. Recent studies have f ...[more]

PMID: 31680725

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Project description:Endometrial cancer (EC) can easily be cured when diagnosed at an early stage. However, advanced and metastatic EC is a common disease, affecting more than 15,000 patients per year in the United Sates. Only limited treatment options were available until recently, with a taxane-platinum combination as the gold standard in first-line setting and no efficient second-line chemotherapy or hormone therapy. EC can be split into four molecular subtypes, including hypermutated cases with POLE mutations and 25-30% harboring a microsatellite instability (MSI) phenotype with mismatch repair deficiency (dMMR). These tumors display a high load of frameshift mutations, leading to increased expression of neoantigens that can be targeted by the immune system, including (but not limited) to T-cell response. Recent data have demonstrated this impact of programmed death 1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors on chemo-resistant metastatic EC. The uncontrolled KEYNOTE-158 and GARNET trials have shown high response rates with pembrolizumab and dostarlimab in chemoresistant MSI-high tumors. Most responders experiment long responses that last more than one year. Similar, encouraging results were obtained for MMR proficient (MMRp) cases treated with a combination of pembrolizumab and the angiogenesis inhibitor lenvatinib. Approvals have, thus, been obtained or are underway for EC with immune checkpoint inhibitors (ICI) used as monotherapy, and in combination with antiangiogenic agents. Combinations with other targeted therapies are under evaluation and randomized studies are ongoing to explore the impact of ICI-chemotherapy triplets in first-line setting. We summarize in this review the current knowledge of the immune environment of EC, both for MMRd and MMRp tumors. We also detail the main clinical data regarding PD-1/PD-L1 inhibitors and discuss the next steps of development for immunotherapy, including various ICI-based combinations planned to limit resistance to immunotherapy.

Dataset Information

Postablation Immune Microenvironment: Synergy between Interventional Oncology and Immuno-oncology.

Publications

Postablation Immune Microenvironment: Synergy between Interventional Oncology and Immuno-oncology.

Similar Datasets

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