Exploring immunotherapy in colorectal cancer

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: July 16, 2022

Chemotherapy combined with or without targeted therapy is the fundamental treatment for metastatic colorectal cancer (mCRC). Due to adverse effects of chemotherapeutic drugs and biological characteristics tumor cells, it difficult make breakthroughs in traditional strategies. The immune checkpoint blockades (ICB) has made significant progress advanced malignant tumors, patients who benefit from this may obtain a long-lasting response. Unfortunately, immunotherapy only effective limited number microsatellite instability-high (MSI-H), segment initial responders can subsequently develop acquired resistance. From September 4, 2014, first anti-PD-1/PD-L1 drug Pembrolizumab was approved by FDA second-line melanoma. Subsequently, mCRC 2017. Immunotherapy rapidly developed past 7 years. in-depth research ICB indicated that mechanism immune-resistance become gradually clear, new predictive biomarkers are constantly emerging. Clinical trials examining effect checkpoints actively carried out, order produce patients. This review summarizes strategies patients, discusses application treatment, outlines potential markers efficacy, lists key results clinical trials, collects recent basic results, provide theoretical basis practical direction

Language: Английский

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Ultrathin Clay Nanoparticles‐Mediated Mutual Reinforcement of Ferroptosis and Cancer Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(9)

Published: Nov. 8, 2023

Ferroptosis-triggered immunogenic cell death (ICD) is widely adopted to potentiate the body's antitumor immunity by catalyzing production of toxic reactive oxygen species (ROS). However, efficacy ferroptosis and immunotherapy greatly restricted intracellular abundant glutathione (GSH) immunosuppressive tumor microenvironment (TME). Herein, a facile bottom-up method for solvent-free synthesis ultrathin manganese (Mn)-based layered double hydroxide nanosheets with high loading efficiency pro-inflammatory cytokine interferon (IFNγ) (IFNγ/uMn-LDHs) proposed mutually reinforce systemic immunity. The introduction ions significantly contributes GSH depletion hydroxyl radical generation, which can be further enhanced IFNγ delivery-induced SLC7A11 downregulation. ICD effect after cooperates intrinsic immunomodulatory property IFNγ/uMn-LDHs facilitate maturation dendritic cells (DCs) priming T cells. secretion from activated CD8

Language: Английский

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Uncovering the complex role of interferon-gamma in suppressing type 2 immunity to cancer

Cytokine, Journal Year: 2023, Volume and Issue: 171, P. 156376 - 156376

Published: Sept. 23, 2023

Language: Английский

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Dysregulation in IFN-γ signaling and response: the barricade to tumor immunotherapy

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 18, 2023

Interferon-gamma (IFN-γ) has been identified as a crucial factor in determining the responsiveness to immunotherapy. Produced primarily by natural killer (NK) and T cells, IFN-γ promotes activation, maturation, proliferation, cytokine expression, effector function immune while simultaneously inducing antigen presentation, growth arrest, apoptosis tumor cells. However, cells can hijack signaling pathway mount resistance: rather than increasing antigenicity succumbing death, acquire stemness characteristics express immunosuppressive molecules defend against antitumor immunity. In this review, we summarize potential mechanisms of resistance occurring at two critical stages: disrupted signal transduction along IFNG/IFNGR/JAK/STAT pathway, or preferential expression specific interferon-stimulated genes (ISGs). Elucidating molecular through which develop help identify promising therapeutic targets improve immunotherapy, with broad application value conjugation targeted, antibody cellular therapies.

Language: Английский

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Quercetin induces ferroptosis in gastric cancer cells by targeting SLC1A5 and regulating the p-Camk2/p-DRP1 and NRF2/GPX4 Axes

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 213, P. 150 - 163

Published: Jan. 6, 2024

Language: Английский

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Beyond the Barrier: Unraveling the Mechanisms of Immunotherapy Resistance

Annual Review of Immunology, Journal Year: 2024, Volume and Issue: 42(1), P. 521 - 550

Published: Feb. 21, 2024

Immune checkpoint blockade (ICB) induces a remarkable and durable response in subset of cancer patients. However, most patients exhibit either primary or acquired resistance to ICB. This arises from complex interplay diverse dynamic mechanisms within the tumor microenvironment (TME). These include genetic, epigenetic, metabolic alterations that prevent T cell trafficking site, induce immune dysfunction, interfere with antigen presentation, drive heightened expression coinhibitory molecules, promote survival after attack. The TME worsens ICB through formation immunosuppressive networks via inhibition, regulatory metabolites, abnormal resource consumption. Finally, patient lifestyle factors, including obesity microbiome composition, influence resistance. Understanding heterogeneity cellular, molecular, environmental factors contributing is crucial develop targeted therapeutic interventions enhance clinical response. comprehensive overview highlights key may be clinically translatable.

Language: Английский

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Recent developments in immunotherapy for gastrointestinal tract cancers

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Aug. 9, 2024

The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. role immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in treatment advanced perioperative GI Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen unselected gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), esophageal (EC). In addition, encouraging performance claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy later-line cancers brings new hope cell solid tumour treatment. Nevertheless, remains yet precise, researchers are dedicated to further maximising optimising efficacy. This review summarises important research, latest progress, future directions including EC, G/GEJC, CRC.

Language: Английский

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PHLDA2-mediated phosphatidic acid peroxidation triggers a distinct ferroptotic response during tumor suppression

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(4), P. 762 - 777.e9

Published: Feb. 2, 2024

Language: Английский

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Current progress and future perspectives of neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 9, 2022

Immunotherapies, especially the programmed cell death 1/programmed ligand 1 (PD-1/PD-L1) inhibitors, have revolutionized therapeutic strategies of various cancers. As for colorectal cancer (CRC), current clinical application PD-1/PD-L1 inhibitors are mainly used according to mutation pattern, which is categorized into deficient mismatch repair (dMMR)/high levels microsatellite instability (MSI-H) and proficient (pMMR), or non-high (non-MSI-H). been proven favorable outcomes against dMMR/MSI-H CRC because more T-cell infiltration tumor tissues. Nevertheless, effectiveness in pMMR/non-MSI-H still uncertain. Because quite-lower proportion CRC, reported combine with other antitumor treatments including chemotherapy, radiotherapy, targeted therapy better effect recent trials. Neoadjuvant therapy, chemotherapy not only can reduce stage but also benefit from local control, improve symptoms quality life. Adding immunotherapy neoadjuvant may change treatment strategy primary resectable some metastatic CRC. In this review, we focus on development anti-PD-1/PD-L1 discuss future perspectives

Language: Английский

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Single cell dynamics of tumor specificity vs bystander activity in CD8+ T cells define the diverse immune landscapes in colorectal cancer

Cell Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Nov. 15, 2023

Abstract CD8 + T cell activation via immune checkpoint blockade (ICB) is successful in microsatellite instable (MSI) colorectal cancer (CRC) patients. By comparison, the success of immunotherapy against stable (MSS) CRC limited. Little known about most critical features cells that together determine diverse landscapes and contrasting ICB responses. Hence, we pursued a deep single mapping on transcriptomic receptor (TCR) repertoire levels patient cohort, with additional surface proteome validation. This revealed dynamics are underscored by complex interactions between interferon-γ signaling, tumor reactivity, TCR repertoire, (predicted) antigen-specificities, environmental cues like gut microbiome or colon tissue-specific ‘self-like’ features. MSI showed tumor-specific reminiscent canonical ‘T hot’ tumors, whereas MSS exhibited unspecific bystander-like was accompanied inflammation ‘pseudo-T tumors. Consequently, overlapping phenotypic differed dramatically their antigen-specificities. Given high discriminating potential for features/specificities, used tumor-reactive signaling modules to build bulk transcriptome classification “Immune Subtype Classification” (ISC) successfully distinguished various tumoral prognostic value predicted responses Thus, deliver unique map drives novel landscape classification, relevance decision-making.

Language: Английский

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