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Transmembrane glycoprotein BSG serves a dual role as a prognostic and immunological modulator in the tumor microenvironment of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a predominant and lethal subtype of non-small cell lung cancer, with a lack of reliable prognostic biomarkers to guide clinical management. Basigin (BSG) has been implicated in tumor progression across multiple cancers, yet its expression pattern, prognostic significance, and underlying mechanisms in LUAD remain incompletely elucidated. METHODS: We integrated multi-omics data from TCGA, GTEx, CCLE, and GEO databases to analyze BSG expression profiles. Clinical correlations were assessed via Kruskal-Wallis tests. Prognostic value was determined using K

Multifunctional nanoplatforms deciphering immune resistance in bone tumors: cooperative delivery, immune reprogramming and microenvironment remodeling.

Bone tumors, encompassing primary sarcomas such as osteosarcoma and secondary skeletal metastases from carcinomas, present a stubborn clinical problem. Their treatment is hampered by three interconnected barriers: the physical impediment of a mineralized matrix that restricts drug access, a profoundly immunosuppressive microenvironment that inactivates antitumor immunity, and the lack of endogenous tissue regeneration following therapeutic intervention. Conventional modalities-including systemic chemotherapy, surgical resection, and even modern immunotherapies-often yield disappointing results

CARS1 as a Prognostic Biomarker and Candidate Therapeutic Vulnerability in Hepatocellular Carcinoma: Insights Into Tumor Progression and the Immune Microenvironment.

BACKGROUND: Cysteinyl-tRNA synthetase 1 (CARS1) has been included in ferroptosis-related prognostic signatures, but its clinicopathological relevance, cellular functions, and relationship with the immune microenvironment in hepatocellular carcinoma (HCC) remain incompletely characterized. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset were integrated with corresponding data from an institutional HCC tissue cohort of 60 patients. CARS1 expression was evaluated by immunohistochemistry, and immune infiltration was examine

Development of combinatorial immunotherapy for patients with advanced gastric cancer from the perspective of immunosuppressive mechanisms in the tumor microenvironment.

Combinatorial immunotherapy using anti-programmed cell death 1 (PD-1) monoclonal antibody (mAb) is being developed to overcome the limited efficacy of monotherapy with anti-PD-1 mAb for patients with advanced gastric cancer (GC). Anti-PD-1 mAb exhibits clinical efficacy by enhancing the function of cytotoxic T lymphocyte (CTL) through the inhibition of the PD-1 pathway;however, there are various immunosuppressive mechanisms that inhibit CTL function, as well as the PD-1 pathway in the tumor microenvironment (TME). Immune suppressive cells and expression of the inhibitory immune checkpoint mole…

Exploring the possible mechanism of low-dose naloxone exposure improving the immune microenvironment of gastric cancer tumors.

INTRODUCTION: Gastric cancer, one of the most common cancers of the digestive tract, has high incidence and mortality rates. Until recently, surgery has been the most effective method of treatment for gastric cancer. Surgery, however, inevitably results in dysfunction of the autonomic nervous system, entry of tumor cells into the bloodstream, and immunosuppression during the perioperative period, all of which increase the risk of complications in patients with gastric cancer. Opioid receptors play an important role in the proliferation and secretion of cytotoxic factors by immune cells. Opiate

Metabolic-immune axis in the tumor microenvironment: a new strategy for prognostic assessment and precision therapy in DLBCL and FL.

Diffuse large B-cell lymphoma and follicular lymphoma exhibit complex metabolic and immune microenvironments that influence disease progression and treatment response. Metabolic reprogramming, including glycolysis, amino acid, and lipid metabolism, supports tumor growth while suppressing anti-tumor immunity. Immune components such as tumor-infiltrating lymphocytes and checkpoint molecules (PD-L1, LAG-3, TIM-3) further modulate prognosis. Elevated tumor metabolic volume and glycolytic activity correlate with aggressive disease and poor outcomes. Conversely, high TIL density often predicts bette

Nerofe+ldDox releases c-Jun from nuclear ST2 to reprogram the immune microenvironment in mtKRAS tumors.

BACKGROUND/OBJECTIVES: Mutant KRAS (mtKRAS) tumors are highly immunosuppressive, largely through secretion of IL-10 and TGF-β2, which prevent immune cell infiltration. Nerofe (dTCApFs), a peptide derivative of Tumor Cell Apoptosis Factor, induces endoplasmic reticulum stress and modulates immune signaling through the T1/ST2 receptor, which is overexpressed in mtKRAS tumors. We evaluated whether combining Nerofe with low-dose doxorubicin (ldDox) could remodel the immune microenvironment and overcome tumor immunosuppression. METHODS: In vitro experiments were performed in PANC-1 pancreatic aden

Understanding the Tumor Microenvironment in Melanoma Patients with In-Transit Metastases and Its Impacts on Immune Checkpoint Immunotherapy Responses.

Melanoma is the leading cause of global skin cancer-related death and currently ranks as the third most commonly diagnosed cancer in Australia. Melanoma patients with in-transit metastases (ITM), a type of locoregional metastasis located close to the primary tumor site, exhibit a high likelihood of further disease progression and poor survival outcomes. Immunotherapies, particularly immune checkpoint inhibitors (ICI), have demonstrated remarkable efficacy in ITM patients with reduced occurrence of further metastases and prolonged survival. The major challenge of immunotherapeutic efficacy lies

BAP1 Deficiency Inflames the Tumor Immune Microenvironment and Is a Candidate Biomarker for Immunotherapy Response in Malignant Pleural Mesothelioma.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare and universally lethal malignancy with limited treatment options. Immunotherapy with immune checkpoint inhibitors (ICIs) has recently been approved for unresectable MPM, but response to ICIs is heterogeneous, and reliable biomarkers for prospective selection of appropriate subpopulations likely to benefit from ICIs remain elusive. METHODS: We performed multiscale integrative analyses of published primary tumor data set from The Cancer Genome Atlas (TCGA) and the French cohort E-MTAB-1719 to unravel the tumor immune microenvironment

In ovarian cancer maraviroc potentiates the antitumoral activity and further inhibits the formation of a tumor-promoting microenvironment by trabectedin.

Ovarian cancer (OC) is the fifth most frequent cause of cancer-related death in women. Chemotherapy agent trabectedin, affecting cancer cells and tumor microenvironment, has been approved for the treatment of relapsed platinum-sensitive OC patients. CCR5-antagonist maraviroc inhibits tumor growth, metastasis, and enhances the antitumoral activity of DNA-damaging drugs. Here, we found that OC cells expressed CCR5 receptor but did not secret CCR5-ligands. Maraviroc treatment did not affect OC cell viability, but strongly potentiated the antiproliferative activity, apoptosis induction, cell cycle…

STING activation reprograms the microenvironment to sensitize NF1-related malignant peripheral nerve sheath tumors for immunotherapy.

Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene that encodes neurofibromin, a RAS GTPase-activating protein. Inactivat … eat inoperable, undruggable cancers like MPNST, but successful outcomes require an immune cell-rich tumor microenvironment. While MPNSTs are noninflamed "cold" tumors, here, we converted MPNSTs into T cell-inflamed "hot" tumors by activating stimulator of IFN genes (STING) signaling. Mouse genetic and human xenograft MPNST models treated with a STING agonist plus ICB ex …

Identification of ESM1 as a Potential Biomarker Involving Drug Sensitivity and the Tumor Immune Microenvironment that Promotes Proliferation of Melanoma.

ESM1 may play a role in human cancers, but its role in melanoma remains unclear. This study investigated ESM1 expression in Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and confirmed it through immunohistochemistry (IHC) and Western blotting (WB). Using the ESM1 gene expression levels, we divided TCGA samples into high and low-expression groups and identified differentially expressed genes (DEGs) between them. We then performed GO and KEGG enrichment analyses on these DEGs and explored the immune landscape while identifying anti-tumor drugs. ESM1 was found to be highl

The expression profiles of CD47 in the tumor microenvironment of salivary gland cancers: a next step in histology-driven immunotherapy.

BACKGROUND: Salivary gland carcinomas (SGC) are extremely rare malignancies with only limited treatment options for the metastatic phase of the disease. Treatment with anti-CD47 antibodies could represent a potent therapy for SGCs by promoting the phagocytic clearance of tumor cells through various mechanisms. However, the efficacy of anti-CD47 therapy is largely dependent on the expression of CD47 within the tumor microenvironment (TME). MATERIALS AND METHODS: In 43 patients with SGC, we were the first to investigate the CD47 expression in both tumor cells and tumor-infiltrating immune cells…

Red Light Phototherapy Using Light-Emitting Diodes Inhibits Melanoma Proliferation and Alters Tumor Microenvironments.

BACKGROUND: Total annual cancer rates have decreased due to improved treatment and prevention. However, the incidence of melanoma is rising, and not all patients respond to immune and targeted approaches. Therefore, we sought to determine the efficacy of red light (RL) phototherapy in preclinical models of melanoma. METHODS: Melanoma cells (A375, B16F10, MNT-1) were irradiated with RL. Melanoma proliferation, apoptosis, oxidative stress, and p53 phosphorylation were measured in vitro. In C57BL/6 mice, phototherapy safety, B16F10 tumor growth, and immunocyte infiltration were assessed followin

Tumoral microenvironment prevents de novo asparagine biosynthesis in B cell lymphoma, regardless of ASNS expression.

Depletion of circulating asparagine with l-asparaginase (ASNase) is a mainstay of leukemia treatment and is under investigation in many cancers. Expression levels of asparagine synthetase (ASNS), which catalyzes asparagine synthesis, were considered predictive of cancer cell sensitivity to ASNase treatment, a notion recently challenged. Using [U-13C5]-l-glutamine in vitro and in vivo in a mouse model of B cell lymphomas (BCLs), we demonstrated that supraphysiological or physiological concentrations of asparagine prevent de novo asparagine biosynthesis, regardless of ASNS expression levels. Ove

A Systematic Pan-Cancer Analysis of YY1 Aberrations and their Relationship with Clinical Outcome, Tumor Microenvironment, and Therapeutic Targets.

Yin-Yang 1 (YY1) has a crucial function in the development of several malignancies, according to recent research. However, nothing is known about its aberrant expression and prognostic significance in human pan-cancer. We first explored the potential carcinogenic effect of YY1 in 33 cancers using the cancer genome atlas (TCGA) project and gene expression omnibus (GEO) datasets in this research. Then, we contained a variety of elements, for instance, gene expression, the state of survival, gene alterations, protein phosphorylation, immune infiltration, and related cellular pathways, and used a

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… The activity of a number of tumor-infiltrating immune cells has been reported to be regulated by tumor-associated fibroblasts in the stroma of the tumor microenvironment. … The tumor microenvironment contained a variety of cells. Among them, infiltrating immune cells account for a large proportion. …

A Tumor Microenvironments-Adapted Polypeptide Hydrogel/Nanogel Composite Boosts Antitumor Molecularly Targeted Inhibition and Immunoactivation.

Various macro/microscopic biomaterials have been developed for controlled drug delivery in the combination therapy of malignancies. However, uncertain loading ratio, release sequence, and spatiotemporal distribution of drugs hinder their synergistic therapeutic effects and clinical applications. In this work, a tumor microenvironments-adapted composite consisting of a thermosensitive hydrogel and a reactive oxygen species (ROS)-responsive nanogel is developed for precisely sequential drug release to enhance molecularly targeted therapy and amplify immune activation. LY3200882 (LY), a selective…

The circuitry of the tumor microenvironment in adult and pediatric Hodgkin lymphoma: cellular composition, cytokine profile, EBV, and exosomes.

BACKGROUND: Classical Hodgkin lymphoma (cHL) is a unique lymphoid malignancy with a tumor microenvironment (TME) consisting of a small number of neoplastic-Hodgkin and Reed-Sternberg (H-RS) cells (<1%), surrounded by a large number of nonneoplastic infiltrating immune cells (>90%). The TME of cHL critically depends on immune cells to support tumor growth as H-RS cells cannot survive and proliferate in isolation. RECENT FINDINGS: Programmed cell death protein 1 (PD-1) ligand expressed on H-RS cells inhibits the clearance of tumor by causing T-cell exhaustion. Nivolumab and pembrolizumab, PD-1 …

Prognostic and clinicopathological significance of PD-1/PD-L1 expression in the tumor microenvironment and neoplastic cells for lymphoma.

BACKGROUND: Recently, unprecedented clinical efficacy was observed during treatment of many solid tumors because of the introduction of programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) immune checkpoint inhibitors. Preliminary clinical data indicates that checkpoint inhibition also represents a promising therapeutic strategy for certain lymphoid malignancies. However, PD-1/PD-L1 expression levels on neoplastic cells and in the tumor microenvironment vary among subtypes and their prognostic implications remain uncertain. MAIN BODY: Here, we review the clinicopathological…