Liver tumour immune microenvironment subtypes and neutrophil heterogeneity

Nature, Год журнала: 2022, Номер 612(7938), С. 141 - 147

Опубликована: Ноя. 9, 2022

Язык: Английский

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Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy

Journal of Hepatology, Год журнала: 2023, Номер 78(4), С. 770 - 782

Опубликована: Янв. 26, 2023

Язык: Английский

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CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers

Science, Год журнала: 2023, Номер 381(6657), С. 515 - 524

Опубликована: Авг. 3, 2023

Tumor microenvironments (TMEs) influence cancer progression but are complex and often differ between patients. Considering that microenvironment variations may reveal rules governing intratumoral cellular programs disease outcome, we focused on tumor-to-tumor variation to examine 52 head neck squamous cell carcinomas. We found macrophage polarity-defined by

Язык: Английский

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Cuproptosis-Related Risk Score Predicts Prognosis and Characterizes the Tumor Microenvironment in Hepatocellular Carcinoma

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июль 11, 2022

Aims Cuproptosis is a recently identified form of programmed cell death; however, its role in hepatocellular carcinoma (HCC) remains unclear. Methods A set bioinformatic tools was integrated to analyze the expression and prognostic significance ferredoxin 1 ( FDX1 ), key regulator cuproptosis. cuproptosis-related risk score (CRRS) developed via correlation analyses, least absolute shrinkage selection operator (LASSO) Cox regression, multivariate regression. The metabolic features, mutation signatures, immune profile CRRS-classified HCC patients were investigated, CRRS therapy guidance analyzed. Results significantly downregulated HCC, high associated with longer survival time. high-CRRS group showed lower overall (OS) enriched cancer-related pathways. Mutation analyses revealed that had mutational frequency some tumor suppressors such as protein P53 TP53 ) Breast-cancer susceptibility gene (BRCA1)-associated BAP1 low catenin beta CTNNB1 ). Besides, an increase protumor infiltrates checkpoints. Moreover, area under curve (AUC) values predicting efficiency sorafenib non-responsiveness transcatheter arterial chemoembolization (TACE) reached 0.877 0.764, respectively. Significance signature helpful prediction guiding treatment for patients.

Язык: Английский

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Managing Resistance to Immune Checkpoint Inhibitors in Lung Cancer: Treatment and Novel Strategies

Journal of Clinical Oncology, Год журнала: 2022, Номер 40(6), С. 598 - 610

Опубликована: Янв. 5, 2022

A proportion of patients with lung cancer experience long-term clinical benefit immune checkpoint inhibitors (ICIs). However, most develop disease progression during treatment or after discontinuation. Definitions resistance are heterogeneous according to different and biologic features. Primary acquired resistance, related tumor-intrinsic tumor-extrinsic mechanisms, identified previous response patterns timing occurrence. The determine differential approaches. To date, several combination therapies under development delay prevent the occurrence ICIs, including blockade coinhibitory signals, activation those costimulatory functions, modulation tumor microenvironment, targeting T-cell priming. Tailoring specific treatments distinctive mechanisms would be ideal improve design results trial. In this review, we reviewed available evidence on definitions, management ICIs in cancer. We also data novel strategies investigation setting.

Язык: Английский

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Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade

Frontiers in Immunology, Год журнала: 2022, Номер 12

Опубликована: Янв. 7, 2022

In the last decade, treatment of non-small cell lung cancer (NSCLC) has been revolutionized by introduction immune checkpoint inhibitors (ICI) directed against programmed death protein 1 (PD-1) and its ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA-4). spite these improvements, some patients do not achieve any benefit from ICI, inevitably develop resistance to therapy over time. Tumor microenvironment (TME) might influence response immunotherapy due prominent role in multiple interactions between neoplastic cells system. Studies investigating perspective TME pointed out a complex scenario where tumor angiogenesis, soluble factors, suppressive/regulatory elements composing itself participate growth. this review, we point current state knowledge involving relationship components NSCLC as well their with providing an update on novel predictors currently employed ICI new therapeutic targets investigational agents. first place, increasing evidence suggests that represent promising biomarker sensitivity based presence immune-modulating cells, such Treg, myeloid derived suppressor associated macrophages, which are known induce immunosuppressive environment, poorly responsive ICI. Consequently, clinical studies have designed towards pro-immunogenic subsequently improve activity Currently, mostly approach relies association “classic” targeting PD-1/PD-L1 agents molecules, LAG-3 TIM-3. To date, trials already shown results, while multitude prospective ongoing, results significantly future immunotherapy.

Язык: Английский

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Tumor heterogeneity reshapes the tumor microenvironment to influence drug resistance

International Journal of Biological Sciences, Год журнала: 2022, Номер 18(7), С. 3019 - 3033

Опубликована: Янв. 1, 2022

Tumor heterogeneity is one of the hallmarks cancer and a challenge in field oncology.Tumor main cause drug resistance, leading to therapeutic failure.Mechanically, tumor either directly affects targets or shapes microenvironment (TME) by defining transcriptomic phenotypic profiles influence resistance.Tumor evolves spatially temporally during development, constant reprogramming TME.Advances molecular profiling technologies precision oncology platforms have allowed us uncover impact on resistance context TME.In this review, we focus processes which genomic mutations drive mechanisms through reprograms TME affect patient prognosis.

Язык: Английский

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Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Янв. 3, 2023

Abstract Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage cancer, but their efficacy setting unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate a combination ICI (camrelizumab), antiangiogenesis (apatinib), chemotherapy (S-1 ± oxaliplatin) for treatment cancer. The primary endpoints are pathological responses potential biomarkers. Secondary include safety, objective response, progression-free survival, overall survival. Complete major response rates 15.8% 26.3%. Pathological correlate significantly with microsatellite instability status, PD-L1 expression, tumor mutational burden. addition, multi-omics examination reveals several putative biomarkers responses, including RREB1 SSPO mutation, immune-related signatures, peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes dominant subclones, immune microenvironments, receptor repertoires during neoadjuvant immunotherapy. toxicity post-surgery complications limited. These data support further validation ICI- antiangiogenesis-based therapy large randomized trials provide candidate

Язык: Английский

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Cancer-Associated Fibroblasts in Inflammation and Antitumor Immunity

Clinical Cancer Research, Год журнала: 2022, Номер 29(6), С. 1009 - 1016

Опубликована: Ноя. 18, 2022

Abstract Tumor-associated inflammation (TAI) is a feature of essentially all cancers and can confer both tumor-promoting -suppressive functions. Cancer-associated fibroblasts (CAF) comprise one very heterogeneous cellular component the tumor microenvironment characterized by high degree plasticity. Recent single-cell sequencing analyses revealed distinct CAF populations in various human helped to define key subtypes, such as myofibroblastic, inflammatory, antigen-presenting CAFs, with first two being present virtually tumors. Importantly, these three are involved modulate positive negative consequences TAI. The remarkable plasticity CAFs allows them shift phenotypically functionally response environmental changes. In this review, we describe how nurture suppress adaptive immunity. We also summarize recently emerging evidence pertaining tumor-suppressive functions context Finally, therapeutic concepts that aim at modulating or depleting immunosuppressive synergize immunotherapy.

Язык: Английский

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Remodeling of the immune and stromal cell compartment by PD-1 blockade in mismatch repair-deficient colorectal cancer

Cancer Cell, Год журнала: 2023, Номер 41(6), С. 1152 - 1169.e7

Опубликована: Май 11, 2023

Язык: Английский

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