Chromosomal instability (CIN) is a driver of cancer metastasis, yet the extent to which this effect depends on the immune system remains unknown. Using ContactTracing-a newly developed, validated and benchmarked tool to infer the nature and conditional dependence of cell-cell interactions from single-cell transcriptomic data-we show that CIN-induced chronic activation of the cGAS-STING pathway promotes downstream signal re-wiring in cancer cells, leading to a pro-metastatic tumour microenvironment. This re-wiring is manifested by type I interferon tachyphylaxis selectively downstream of STING and a corresponding increase in cancer cell-derived endoplasmic reticulum (ER) stress response. Reversal of CIN, depletion of cancer cell STING or inhibition of ER stress response signalling abrogates CIN-dependent effects on the tumour microenvironment and suppresses metastasis in immune competent, but not severely immune compromised, settings. Treatment with STING inhibitors reduces CIN-driven metastasis in melanoma, breast and colorectal cancers in a manner dependent on tumour cell-intrinsic STING. Finally, we show that CIN and pervasive cGAS activation in micronuclei are associated with ER stress signalling, immune suppression and metastasis in human triple-negative breast cancer, highlighting a viable strategy to identify and therapeutically intervene in tumours spurred by CIN-induced inflammation.
Background: Primary liver cancer, particularly hepatocellular carcinoma, is one of the most common gastrointestinal cancers. An increasing number of studies indicate that nanomaterials play a significant role in the diagnosis and treatment of liver cancer. However, despite the extensive and diverse research on nanomaterials and liver cancer, bibliometric studies in this field have not yet been reported.
Background: Gastric cancer (GC) shows limited response to immune checkpoint inhibitors due to its complex tumor immune microenvironment (TIME). This study explores the functions of various immune cells in the complex TIME in GC.
Methods: We assessed CD8 + T-cell infiltration of GC tissues by immunohistochemistry, and performed single-cell RNA sequencing (scRNA-seq) of tumor and normal tissues from 34 patients with GC.
Background: Small cell lung cancer (SCLC) is a highly fatal malignancy, the complex tumor microenvironment (TME) is a critical factor affecting SCLC progression. Cancer-associated fibroblasts (CAFs) are crucial components of TME, yet their role in SCLC and the underlying mechanisms during their interaction with SCLC cells remain to be determined.
Methods: Microenvironmental cell components were estimated using transcriptome data from SCLC tissue available in public databases, analyzed with bioinformatic algorithms.
Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors are promising for treating tumors but have limited efficacy due to the immunosuppressive tumor microenvironment. In this study, we develop an orchestrated nanoparticle system using modular peptide assemblies, where the co-assembled sequences are designed for the specific binding to the hydrophobic and hydrophilic domains, guiding the assembly process and enabling the customization of nanoparticle properties. We exploit the modularity of this platform to integrate a hydrophobic ferroptosis precursor, an IDO1 inhibitor, and a hydrophilic peptidic PD-L1 antagonist for optimizing therapeutic outcomes through ferroptosis-enhanced tumor immunotherapy.
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:
The efficacy and safety of chimeric antigen receptor (CAR) T cell therapy is still inconclusive in solid tumor treatment. Recently, nanotechnology has emerged as a potent strategy to reshape CAR-T cell therapy with promising outcomes. This review aims to discuss the significant potential of nano-engineered CAR-T cell therapy in addressing existing challenges, including CAR-T cell engineering evolution, tumor microenvironment (TME) modulation, and precise CAR-T cell therapy (precise targeting, monitoring, and activation), under the main consideration of clinical translation.
