Evolving Field of Immunotherapy: Pioneering New Paths in Small-Cell Lung Cancer

JCO Oncology Practice, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Small-cell lung cancer (SCLC) is an aggressive form of that displays rapid proliferation and early metastatic potential. It accounts for approximately 15% cancers strongly associated with tobacco carcinogens. Despite patients' initial response to systemic therapy, the majority develop resistance relapse. The outcomes patients SCLC are poor, prompting need new therapies. Over past decade, treatment landscape NSCLC (non-small cell cancer) has significantly changed immergence novel targeted therapies immunotherapies. However, inroads these into have posed significant challenges due its molecular genomic heterogeneity. this disease, promising first-in-class immunomodulatory agents emerged currently undergoing extensive research. Herein, we review current paradigm immunotherapy in discuss future directions evolving field.

Language: Английский

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Targeting HVEM-GPT2 axis: a novel approach to T cell activation and metabolic reprogramming in non-small cell lung cancer therapy

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(3)

Published: Feb. 4, 2025

The modulation of tumor microenvironments through immune checkpoint pathways is pivotal for the development effective cancer immunotherapies. This study aims to explore role HVEM in non-small cell lung (NSCLC) microenvironment. datasets this were directly downloaded from Cancer Genome Atlas (TCGA). Single-cell data sourced Tumor Immune Hub (TISCH). Multiplex immunohistochemistry (mIHC) was used cellular composition and spatial distribution microenvironment KO mice bearing mouse also evaluated. Co-cultured system phenotype assays facilitated examination Jurkat T cells' effect on A549 H1299 cells. Quantitative PCR Western blotting determined gene protein expression, respectively, respiration measured oxygen consumption rate (OCR) assays. Lung cells co-cultured with xenografted into nude evaluate growth metastatic potential. Next, RNA-seq, COIP, Dual-luciferase reporter experiment, CHIP-seq potential underlying mechanism. In our study, we investigated NSCLC its implications immunotherapy. Crucially, HVEM, part necrosis factor receptor superfamily, influences activation, potentially impacting immunotherapeutic outcomes. Using TIDE algorithm, results showcased a link between levels dysfunction patients. Delving deeper microenvironment, found predominantly expressed subpopulations. CD8 + CD4 indicated better prognosis adenocarcinoma tissue microarray using multiplex immunohistochemistry. Activated cells, particularly line, significantly inhibited progression, reducing both proliferation invasion capabilities lines. vivo models reinforced these observations. Manipulating expression revealed essential survival activation. addition, animal experiments importance maintaining activated peripheral immunity inflamed local Furthermore, suggest that metabolic reprogramming, transitioning oxidative phosphorylation aerobic glycolysis. RNA sequencing illuminated relationship GPT2, an enzyme tied amino acid metabolism energetics. Subsequent confirmed HVEM's influence activation mediated regulation GPT2. GATA1 validated regulate Our establishes functionality dynamics, pinpointing HVEM-GPT2 axis as promising target therapy.

Language: Английский

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Why PD-L1 expression varies between studies of lung cancer: results from a Bayesian meta-analysis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 4, 2025

PD-L1 expression is an important biomarker for the management of non-small cell lung cancer (NSCLC) but has been highly heterogeneous across studies. We developed a statistical model to reconcile conflicting estimates prevalence by accounting between-study variation in test sensitivity, specimen age, and laboratory count. In doing so, we obtained refined identified differences histological subtype, mutational status, stage. Across 92 studies published between 2015 2023, detectability declined with increasing age while consistency detection rates was greater incorporating data from higher number laboratories. Using 22C3 antibody as benchmark, predicted that 58.3% (95% CrI 49.8–66.1%) 27.0% 21.2–33.1%) NSCLC will have tumour proportion scores at ≥ 1% 50% threshold. lower EGFR-mutated ALK, KRAS, MET, ROS1, RET alterations. more common later-stage disease. Overall, this work highlights continuing challenge testing. Although underlying varies population based on tumour-related factors, controllable testing parameters also account variations prevalence.

Language: Английский

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Evolving Paradigms in Lung Cancer: Latest Trends in Diagnosis, Management, and Radiopharmaceuticals

Seminars in Nuclear Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Radiation combined with immune checkpoint inhibitors for unresectable locally advanced non-small cell lung cancer: synergistic mechanisms, current state, challenges, and orientations

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 23, 2023

Until the advent of immune checkpoint inhibitors (ICIs), definitive radiotherapy (RT) concurrently with chemotherapy was recommended for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC). The trimodality paradigm consolidation ICIs following concurrent chemoradiotherapy has been standard care since PACIFIC trial. Preclinical evidence demonstrated role RT in cancer-immune cycle and synergistic effect combined (iRT). However, exerts a double-edged on immunity combination strategy still could be optimized many areas. In context LA-NSCLC, modality, choice, timing, duration ICIs, oncogenic addicted tumors, patient selection, novel strategies require further investigation. Targeting these blind spots, approaches are being investigated to cross borders PACIFIC. We discussed development history iRT summarized updated rationale effect. then available research data efficacy toxicity LA-NSCLC cross-trial comparisons eliminate barriers. Progression during after therapy regarded as distinct resistance scenario from primary or secondary subsequent management which also discussed. Finally, based unmet needs, we probed into challenges, strategies, auspicious orientations optimize LA-NSCLC. this review, focus underlying mechanisms recent advances an emphasis future challenges directions that warrant Taken together, is proven potential multiple promising improve efficacy. Video Abstract.

Language: Английский

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Circulating biomarkers as predictors of response to immune checkpoint inhibitors in NSCLC: Are we on the right path?

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 197, P. 104332 - 104332

Published: April 4, 2024

Immune checkpoints inhibitors (ICIs) have markedly improved the therapeutic management of advanced NSCLC and, more recently, they demonstrated efficacy also in early-stage disease. Despite better survival outcomes with ICIs compared to standard chemotherapy, a large proportion patients can derive limited clinical benefit from these agents. So far, few predictive biomarkers, including programmed death-ligand 1 (PD-L1), been introduced practice. Therefore, there is an urgent need identify novel biomarkers select for immunotherapy, improve and avoid unnecessary toxicity. A deeper understanding mechanisms involved antitumor immunity advances field liquid biopsy led identification wide range circulating that could potentially predict response immunotherapy. Herein, we provide updated overview focusing on emerging data studies describing modern technologies used their detection.

Language: Английский

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Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 22, 2024

Abstract A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) adenocarcinoma (NCI-H1437) as cancer. In comparison to gefitinib, Initial biological assessments revealed that several exhibited potent anti-proliferative these lines. Notably, 7a 7j demonstrated most pronounced effects, with an IC 50 value 3.94 ± 0.17 µmol L −1 (NCI-H1299), 3.16 0.11 (A549), 1.83 0.13 , 3.84 0.22 3.86 0.38 1.69 0.25 . These two could inhibit colony formation migration ability H1299 cells, induce apoptosis in cells. Acute toxicity experiments on mice compound low mice. Based results, it is proposed potentially be developed drugs treatment

Language: Английский

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Advancing gastric cancer treatment: nanotechnology innovations and future prospects

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Nov. 20, 2024

Gastric cancer (GC) is the fifth most common worldwide, particularly prevalent in Asia, especially China, where both its incidence and mortality rates are significantly high. Meanwhile, nanotechnology has demonstrated great potential treatment of GC. In particular, nanodrug delivery systems have improved therapeutic efficacy targeting through various functional modifications, such as peptides, tumor microenvironment responsiveness, instrument-based methods. For instance, silica (SiO2) excellent biocompatibility can be used a drug carrier, with porous structure enhancing loading capacity. Polymer nanoparticles regulate release mechanisms by altering material composition preparation Lipid efficiently encapsulate hydrophilic drugs promote cellular uptake, while carbon-based biosensors delivery. Targets integrins, HER2 receptors, been to improve GC treatment. Nanodrug techniques not only enhance capabilities but also selectively target cells. Currently, there lack systematic summarization synthesis regarding relationship between treatment, which some extent hinders researchers clinicians from searching for referencing related studies, thereby reducing work efficiency. This study aims systematically summarize existing research on making it easier professionals search reference, promoting further role their clinical applications review discusses functionalized nanocarriers recent years, including surface modifications targeted markers, combination phototherapy, chemotherapy, immunotherapy, along advantages challenges. It examines future prospects nanomaterials The focuses combined application multiple modalities, demonstrating multimodal treatments. Furthermore, thoroughly explores specific challenges that face biocompatibility, control, translation issues, providing outlook developments. Additionally, this emphasizes value feasibility applications, contrasting reviews focus basic research. Through these innovations, we offer new perspectives directions development

Language: Английский

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Tumor mutation burden in the prognosis and response of lung cancer patients to immune-checkpoint inhibition therapies

Translational Oncology, Journal Year: 2023, Volume and Issue: 38, P. 101788 - 101788

Published: Sept. 28, 2023

Immune checkpoint inhibition (ICI) therapies have reshaped the therapeutic landscape in lung cancer management, providing first-time improvements patient response, prognosis, and overall survival. Despite their clinical effectiveness, variability treatment responsiveness, as well drug resistance, led to a compelling need for predictive biomarkers facilitating individualized selection of most efficient approach. Significant progress has been made identification such biomarkers, with tumor mutation burden (ΤΜΒ) appearing leading promising biomarker efficacy ICIs non-small cell (NSCLC) among other tumors. Anti-PD-1/PD-L1 anti-CTLA-4 antibodies extensively studied clinically utilized. However, efficiency these drugs remains unsatisfactory, urging investigation novel inhibitors, those targeting LAG-3, TIM-3, TIGIT VISTA, which could be used either monotherapy or synergistically PD-1/PD-L1 CTLA-4 blockers. Here, we investigate role TMB neoantigens response patients different ICI therapies, specifically focusing on recent immune against VISTA. We further discuss new trends immunotherapies, including CAR T-cell therapy personalized vaccines. also review potential that immunotherapy, PD-L1+ IHC, MSI/dMMR, infiltrating lymphocytes (TILs), microbiome circulating DNA (ctDNA). Finally, limitations challenges each.

Language: Английский

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Exploring the landscape of drug resistance in gastrointestinal cancer immunotherapy: A review

Medicine, Journal Year: 2024, Volume and Issue: 103(2), P. e36957 - e36957

Published: Jan. 12, 2024

Gastrointestinal (GI) cancers pose a significant challenge due to high prevalence and mortality. While advancements in detection conventional treatments have been made, prognosis often remains poor, particularly for advanced-stage cancers. Immunotherapy has emerged as transformative approach, leveraging the body immune system against cancer, including checkpoint inhibitors (ICIs), cancer vaccines, adoptive cell transfer. These modalities shown promise, achieving sustained responses improved survival some patients. However, their efficacy GI is less pronounced, hindered by drug resistance mechanisms that are either intrinsic or acquired over time. This review examines latest understanding of immunotherapy cancers, focusing on ICIs, transfer, along with associated outcomes limitations. It delves into behind resistance, alterations checkpoints, immunosuppressive tumor microenvironment, genetic/epigenetic changes. The role gut microbiome also considered an emerging factor resistance. To combat strategies such enhancing response, targeting modulating explored. underscores potential ferroptosis induction novel approach. Looking forward, it highlights need personalized immunotherapies, influence microbiome, further exploration overcoming challenges persist, continuous evolution research promises innovative could significantly improve patient outcomes.

Language: Английский

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