Inside-Out of Complement in Cancer

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июль 1, 2022

The role of complement in cancer has received increasing attention over the last decade. Recent studies provide compelling evidence that accelerates progression. Despite pivotal fighting microbes, seems to suppress antitumor immunity via regulation host cell tumor microenvironment. Although most link activation extracellular space, discovery intracellular complement, raises question: what is relevance this process for malignancy? Intracellular survival immune cells. Therefore, can be important and growth regardless immunosuppression. On other hand, because (the complosome) indispensable T cells, these functions will essential priming responses. Here, we review with consideration extra pathways spatial distribution proteins tumors periphery our take on potential significance as biomarker target therapy.

Язык: Английский

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Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1

Science Immunology, Год журнала: 2023, Номер 8(89)

Опубликована: Ноя. 17, 2023

Myeloid cells facilitate T cell immune evasion in cancer yet are pliable and have antitumor potential. Here, by cotargeting myeloid activation molecules, we leveraged the compartment as a therapeutic vulnerability mouse models of pancreatic cancer. solid tumors expressed receptors including pattern recognition receptor Dectin-1 TNF superfamily member CD40. In checkpoint inhibitor-resistant cancer, coactivation Dectin-1, via systemic β-glucan therapy, CD40, with agonist antibody treatment, eradicated established induced immunological memory. Antitumor activity was dependent on cDC1s but did not require classical cell-mediated cytotoxicity or blockade molecules. Rather, targeting CD40 drove IFN-γ signaling, which converged to program distinct macrophage subsets tumor responses. Thus, productive surveillance resistant inhibition can be invoked complementary signaling pathways.

Язык: Английский

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Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling

British Journal of Cancer, Год журнала: 2023, Номер 128(6), С. 1117 - 1133

Опубликована: Янв. 11, 2023

Язык: Английский

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Revealing the role of SPP1+ macrophages in glioma prognosis and therapeutic targeting by investigating tumor-associated macrophage landscape in grade 2 and 3 gliomas

Cell & Bioscience, Год журнала: 2024, Номер 14(1)

Опубликована: Март 21, 2024

Abstract Background Glioma is a highly heterogeneous brain tumor categorized into World Health Organization (WHO) grades 1–4 based on its malignancy. The suppressive immune microenvironment of glioma contributes significantly to unfavourable patient outcomes. However, the cellular composition and their complex interplays within environment remain poorly understood, reliable prognostic markers elusive. Therefore, in-depth exploration (TME) identification predictive are crucial for improving clinical management patients. Results Our analysis single-cell RNA-sequencing data from samples unveiled immunosuppressive role tumor-associated macrophages (TAMs), mediated through intricate interactions with cells lymphocytes. We also discovered heterogeneity TAMs, among which group TAMs named TAM-SPP1 demonstrated significant association Epidermal Growth Factor Receptor ( EGFR ) amplification, impaired T cell response survival Furthermore, by leveraging genomic transcriptomic Cancer Genome Atlas (TCGA) dataset, two distinct molecular subtypes different constitution status outcomes were identified. Exploiting differences between these subtypes, we developed four-gene-based model. This model displayed strong associations an elevated level could be used predict anti-tumor prognosis in Conclusion findings illuminated mechanisms that shape gliomas, providing novel insights potential therapeutic targets. holds promise predicting immunotherapy assisting more precise risk stratification Graphical abstract

Язык: Английский

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Transcriptome Analysis Reveals Dynamic Microglial-Induced A1 Astrocyte Reactivity via C3/C3aR/NF-κB Signaling After Ischemic Stroke

Molecular Neurobiology, Год журнала: 2024, Номер 61(12), С. 10246 - 10270

Опубликована: Май 7, 2024

Язык: Английский

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