Prospects and challenges of CAR-T cell therapy combined with ICIs

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: March 20, 2024

Immune checkpoint molecules are a group of expressed on the surface immune cells that primarily regulate their homeostasis. Chimeric antigen receptor (CAR) T cell therapy is an immunotherapeutic technology realizes tumor-targeted killing by constructing synthetic expressing specific antigens through biotechnology. Currently, CAR-T has achieved good efficacy in non-solid tumors, but its treatment solid tumors not yielded desired results. inhibitors (ICIs) combined with novel combination high expectations to defeat tumors. This review addresses challenges and this

Language: Английский

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Predictive Biomarkers for Immunotherapy in Gastric Cancer: Current Status and Emerging Prospects

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15321 - 15321

Published: Oct. 18, 2023

Gastric cancer presents substantial management challenges, and the advent of immunotherapy has ignited renewed hope among patients. Nevertheless, a significant proportion patients do not respond to immunotherapy, adverse events associated with also occur on occasion, underscoring imperative identify suitable candidates for treatment. Several biomarkers, including programmed death ligand-1 expression, tumor mutation burden, mismatch repair status, Epstein–Barr Virus infection, circulating DNA, tumor-infiltrating lymphocytes, have demonstrated potential in predicting effectiveness gastric cancer. However, quest optimal predictive biomarker remains challenging, as each carries its own limitations. Recently, multi-omics technologies emerged promising platforms discovering novel biomarkers that may help selecting likely immunotherapy. The identification reliable holds promise enhancing patient selection improving treatment outcomes. In this review, we aim provide an overview clinically established Additionally, introduce newly reported based studies context thereby contributing ongoing efforts refine stratification strategies.

Language: Английский

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Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 11, 2024

Abstract Cancer diagnosis and management depend upon the extraction of complex information from microscopy images by pathologists, which requires time-consuming expert interpretation prone to human bias. Supervised deep learning approaches have proven powerful, but are inherently limited cost quality annotations used for training. Therefore, we present Histomorphological Phenotype Learning, a self-supervised methodology requiring no labels operating via automatic discovery discriminatory features in image tiles. Tiles grouped into morphologically similar clusters constitute an atlas histomorphological phenotypes (HP-Atlas), revealing trajectories benign malignant tissue inflammatory reactive phenotypes. These distinct can be identified using orthogonal methods, linking histologic, molecular clinical Applied lung cancer, show that they align closely with patient survival, histopathologically recognised tumor types growth patterns, transcriptomic measures immunophenotype. properties maintained multi-cancer study.

Language: Английский

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Histopathological Aspects of the Prognostic Factors for Salivary Gland Cancers

Cancers, Journal Year: 2023, Volume and Issue: 15(4), P. 1236 - 1236

Published: Feb. 15, 2023

Salivary gland cancers (SGCs) are diagnosed using histopathological examination, which significantly contributes to their progression, including lymph node/distant metastasis or local recurrence. In the current World Health Organization (WHO) Classification of Head and Neck Tumors: Glands (5th edition), malignant benign epithelial tumors classified into 21 15 tumor types, respectively. All have potential for particular, mucoepidermoid carcinoma (MEC), adenoid cystic (AdCC), salivary duct carcinoma, not otherwise specified (NOS, formerly known as adenocarcinoma, NOS), myoepithelial epithelial–myoepithelial ex pleomorphic adenoma (PA) relatively prevalent. High-grade transformation is an important aspect progression in SGCs. MEC, AdCC, NOS a distinct grading system; however, universal histological system SGCs has yet been recommended. Conversely, PA considered benign; nonetheless, it should be cautiously treated avoid development metastasizing/recurrent PA. The aim this review describe aspects prognostic factors discuss genes molecules used diagnostic tools that might treatment target future.

Language: Английский

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Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors—A 2023 Update

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5643 - 5643

Published: March 15, 2023

With the aging of population, malignancies are becoming common complications in patients with rheumatoid arthritis (RA), particularly elderly patients. Such often interfere RA treatment. Among several therapeutic agents, immune checkpoint inhibitors (ICIs) which antagonize immunological brakes on T lymphocytes have emerged as a promising treatment option for variety malignancies. In parallel, evidence has accumulated that ICIs associated numerous immune-related adverse events (irAEs), such hypophysitis, myocarditis, pneumonitis, and colitis. Moreover, not only exacerbate pre-existing autoimmune diseases, but also cause de novo rheumatic disease–like symptoms, arthritis, myositis, vasculitis, currently termed irAEs. Rheumatic irAEs differ from classical diseases multiple aspects, should be individualized based severity. Close collaboration oncologists is critical preventing irreversible organ damage. This review summarizes current regarding mechanisms management focus vasculitis. Based these findings, potential strategies against discussed.

Language: Английский

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Adebrelimab plus chemotherapy and sequential thoracic radiotherapy as first-line therapy for extensive-stage small–cell lung cancer (ES-SCLC): a phase II trial

EClinicalMedicine, Journal Year: 2024, Volume and Issue: 75, P. 102795 - 102795

Published: Aug. 23, 2024

Language: Английский

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Gut microbiota as a biomarker and modulator of anti-tumor immunotherapy outcomes

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 28, 2024

Although immune-checkpoint inhibitors (ICIs) have significantly improved cancer treatment, their effectiveness is limited by primary or acquired resistance in many patients. The gut microbiota, through its production of metabolites and regulation immune cell functions, plays a vital role maintaining balance influencing the response to immunotherapies. This review highlights evidence linking specific microbial characteristics increased therapeutic efficacy variety cancers, such as gastrointestinal melanoma, lung cancer, urinary system reproductive suggesting microbiota’s potential predictive biomarker for ICI responsiveness. It also explores possibility enhancing fecal microbiota transplantation, probiotics, prebiotics, synbiotics, postbiotics, dietary modifications. Moreover, underscores need extensive randomized controlled trials confirm value establish guidelines microbiota-targeted interventions immunotherapy. In summary, article suggests that balanced key maximizing immunotherapy benefits calls further research optimize modulation strategies treatment. advocates deeper comprehension complex interactions between host immunity, therapy, aiming more personalized effective treatment options.

Language: Английский

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Engineering metal-organic framework nanoparticles trigger pyroptosis to boost colon cancer immunotherapy

Materials & Design, Journal Year: 2024, Volume and Issue: 238, P. 112731 - 112731

Published: Feb. 1, 2024

Pyroptosis, which is a novel form of immunogenic cell death, plays vital role in antitumor therapy. Zirconium-based metal–organic frameworks (Zr-MOFs) have been applied various treatments. However, the intrinsic these pyroptosis has yet to be determined. Here, Zr-MOF-based nanosystem (DOX@Zr-MOF) was constructed by loading Zr-MOF nanoparticles with chemotherapeutic drug doxorubicin (DOX) synergistically trigger cancer pyroptosis. We found that DOX@Zr-MOF rapidly triggered via activation canonical caspase-3/gasdermin E (GSDME)-dependent pathway, resulting significant suppression CT26 colon tumor growth vitro and vivo. Furthermore, significantly enhanced systemic immune response reprogramming immunosuppressive microenvironment. In addition, combination programmed death-1 (PD-1) immunotherapy strongly improved efficacy tumors. Overall, this work provides promising strategy for pyroptosis-mediated anticancer treatment, may efficiently improve checkpoint blockade-related immunotherapy.

Language: Английский

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Association between the gut microbiota, inflammatory factors, and colorectal cancer: evidence from Mendelian randomization analysis

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: March 18, 2024

Colorectal cancer (CRC) is one of the most common malignant tumors primarily affecting individuals over age 50 years. Recent studies have suggested that dysbiosis gut microbiota, a community microorganisms in human gut, closely associated with occurrence and development CRC. Additionally, inflammatory factors (IFs) also been reported to play significant role However, causal relationships between IFs, CRC remain unclear. In this study, we performed Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) data explore relationship The microbiota GWAS were obtained from MiBioGen while IFs derived comprehensive three independent cohorts. Causal was conducted appropriate instrumental variables (IVs) statistical models. MR revealed negative correlation Lachnospiraceae species risk, positive observed Porphyromonadaceae species, UCG010 genus, Lachnospira Sellimonas genus risk. IL-10 These findings suggest might be an increased risk specific bacterial groups may crucial Using analysis, as well CRC, provide important clues for potential roles regulation factor control prevention treatment

Language: Английский

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Microsatellite instability: A potential game-changer in colorectal cancer diagnosis and treatment

Results in Chemistry, Journal Year: 2024, Volume and Issue: 7, P. 101461 - 101461

Published: Jan. 1, 2024

Colorectal cancer (CRC) is a complicated illness caused by mix of hereditary and environmental factors. It one the most common malignancies worldwide, yet it also curable if detected early. There are three types molecular changes in CRC: chromosomal instability, CpG island methylator phenotype, microsatellite instability (MSI). MSI an uncommon change generated malfunctioning DNA mismatch repair (MMR) system. occurs approximately 15–20% CRC patients. In CRC, has significant prognostic therapeutic implications. MSI-positive patients have better prognosis more likely to react treatment. can be used identify categorise tumours.

Language: Английский

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