FAP upregulates PD-L1 expression in cancer-associated fibroblasts to exacerbate T cells dysfunction and suppress anti-tumor immunity.

FAP-positive cancer-associated fibroblasts (CAFs), recognized as a critical subset of CAFs, have been implicated in fostering an immunosuppressive tumor microenvironment in various cancers. However, their potential mechanisms of immunosuppression, particularly in modulating T cells, remain elusive. In this study, multiple internal cohorts consisting of 328 patients as well as 5 external cohorts were integrated to delineate the association between unfavorable prognosis or therapeutic resistance and FAP CAFs in gastric cancer patients.

CPT1C-positive cancer-associated fibroblast facilitates immunosuppression through promoting IL-6-induced M2-like phenotype of macrophage.

Cancer-associated fibroblasts (CAFs) exhibit remarkable phenotypic heterogeneity, with specific subsets implicated in immunosuppression in various malignancies. However, whether and how they attenuate anti-tumor immunity in gastric cancer (GC) remains elusive. CPT1C, a unique isoform of carnitine palmitoyltransferase pivotal in regulating fatty acid oxidation, is briefly indicated as a protumoral metabolic mediator in the tumor microenvironment (TME) of GC.

Immunosuppressive MFAP2 cancer associated fibroblasts conferred unfavorable prognosis and therapeutic resistance in gastric cancer.

Purpose: To explore the predictive merit of MFAP2 cancer associated fibroblasts (CAFs) infiltration for clinical outcomes and adjuvant chemotherapy or immunotherapy responsiveness in gastric cancer (GC).

Methods: In this study, several independent cohorts were included respectively to dissect the relationship of clinical outcomes, therapeutic responses and tumor microenvironment with different MFAP2 CAFs infiltration. Drug sensitivity analysis was conducted to predict the relationship between MFAP2 CAFs infiltration and targeted drug response.

Sanguinarine induces apoptosis in osteosarcoma by attenuating the binding of STAT3 to the single-stranded DNA-binding protein 1 (SSBP1) promoter region.

Background And Purpose: Osteosarcoma, a primary malignant bone tumour prevalent among adolescents and young adults, remains a considerable challenge despite protracted progress made in enhancing patient survival rates over the last 40 years. Consequently, the development of novel therapeutic approaches for osteosarcoma is imperative. Sanguinarine (SNG), a compound with demonstrated potent anticancer properties against various malignancies, presents a promising avenue for exploration.

Discovery of a potent inhibitor of chaperone-mediated autophagy that targets the HSC70-LAMP2A interaction in non-small cell lung cancer cells.

Background And Purpose: Chaperone-mediated autophagy (CMA) is a selective type of autophagy targeting protein degradation and maintains high activity in many malignancies. Inhibition of the combination of HSC70 and LAMP2A can potently block CMA. At present, knockdown of LAMP2A remains the most specific method for inhibiting CMA and chemical inhibitors against CMA have not yet been discovered.

Versican enrichment predicts poor prognosis and response to adjuvant therapy and immunotherapy in gastric cancer.

Background: Increasing evidence has revealed an important role of versican (VCAN) on various aspects of cancer progression. Here, we assessed the impact of VCAN expression on prognosis and the response to adjuvant therapy and immunotherapy in patients with gastric cancer (GC).

Methods: Four independent cohorts containing 1353 patients with GC, were utilized to investigate the effect of VCAN expression on prognosis and response to adjuvant therapy in GC.

Metastasis Related Epithelial-Mesenchymal Transition Signature Predicts Prognosis and Response to Immunotherapy in Gastric Cancer.

Background: Increasing evidence has revealed the effect of epithelial-mesenchymal transition (EMT) on tumor microenvironment and cancer treatment. However, an EMT-based signature to predict the prognosis and therapeutic effect in gastric cancer (GC) has rarely been established.

Methods: Differentially expressed genes (DEGs) between paired primary gastric and ovarian metastatic tumors were identified through comparative RNA-seq analysis, followed by the construction of metastasis-related EMT signature (MEMTS) based on DEGs and EMT gene set.

Pan-cancer analysis reveals RIPK2 predicts prognosis and promotes immune therapy resistance via triggering cytotoxic T lymphocytes dysfunction.

Background: Receptor-interacting protein kinase 2 (RIPK2, also known as RIP2) was reported to be associated with bacterial infections as well as inflammatory responses. However, the role of RIPK2 in prognosis and immunotherapy response is yet to be elucidated in human pan-cancer.

Methods: In this study, we investigated the expression, gene alteration landscape and prognostic value of RIPK2 in 33 cancers through various databases including Ualcan, cBioportal and Gene Expression Profiling Interactive Analysis 2 (GEPIA2).