NK cells limit the synergistic anti-tumor effect of PD-1 inhibition and βγ-biased IL-2.

Despite its potential as a cancer immunotherapy, wild-type IL-2 is limited by dose-limiting toxicities, including vascular leak syndrome, and its strong activation of regulatory T cells (Tregs), which dampens anti-tumor immunity. These drawbacks are largely driven by IL-2's binding to IL-2Rα, and avoiding this interaction can reduce IL-2-associated toxicities, although it cannot completely eliminate them. To overcome these limitations, βγ-biased IL-2 variants (Non-α-IL-2) have been developed to selectively activate effector T and NK cells.

IL-1R2 promotes tumorigenesis and modulates the tumor immune microenvironment in colorectal cancer.

Colorectal cancer (CRC) continues to be a major global health challenge due to its high incidence and mortality rates, emphasizing the critical need for innovative therapeutic strategies. IL-1R2, a member of the IL-1 receptor family, plays a pivotal role in both tumorigenesis and antitumor immunity. However, its precise role in tumor development and its impact on immune checkpoint inhibitors (ICIs) therapy in CRC remain poorly understood.

Identification of MAGE-A10 specific T cell receptor promising in immunotherapy of hepatocellular carcinoma.

Due to the limitations of current treatment strategies, hepatocellular carcinoma (HCC) continues to impose a severe burden on people's health. In the process of exploring novel therapies, T cell receptor-engineered T cell (TCR-T) therapy has been extensively developed in HCC immunotherapy. Melanoma-associated antigen family A member 10 (MAGE-A10) is a cancer-testis antigen (CTA), specifically expressed on HCC cells.

Enhancing Colorectal Cancer Treatment Through VEGF/VEGFR Inhibitors and Immunotherapy.

Colorectal cancer, ranking as the third most prevalent malignancy globally, substantially benefits from both immunotherapy and VEGF/VEGFR inhibitors. Nevertheless, the use of monotherapy proves inadequate in effectively tackling the heterogeneity of tumors and the intricacies of their microenvironment, frequently leading to drug resistance and immune evasion. This situation underscores the pressing need for innovative strategies aimed at augmenting the effectiveness and durability of treatments.

Identification of HES4 as a novel prognostic marker and therapeutic target in hepatocellular carcinoma.

Hairy and enhancer of Split 4 (HES4) is thought to have a substantial impact on the pathogenesis and progression of malignancies. However, the prognostic significance and mechanism of HES4 have not been reported in Hepatocellular carcinoma (HCC). A comprehensive bioinformatics analysis of HES4 expression, clinicopathological characteristics, tumor microenvironment status, and drug sensitivity were performed based on TCGA, GTEx, and GEO.

Cordycepin enhances the Anticancer efficacy of PD-L1 blockade by modulating the tumor microenvironment of colon cancer.

Background: PD-L1 blockade has been found to be effective in treating multiple malignancies. Combined therapy is proposed to provide better therapeutic effects. Cordycepin, a prominent bioactive compound found in cordyceps, can inhibit the development of various cancers.

Strategies for the enhancement of IL-21 mediated antitumor activity in solid tumors.

Solid tumors significantly impact global health, necessitating enhanced prevention, early diagnosis, and treatment approaches. Tumor immunotherapy, notably through programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1), offers new hope to patients with advanced tumors, although many still do not benefit. Interleukin-21 (IL-21), a cytokine produced by certain immune cells, performs various biological functions by activating the JAK/STAT signaling pathway.

Tregs ST2 deficiency enhances the abscopal anti-tumor response induced by microwave ablation.

Background: Thermal ablation (TA), including radiofrequency ablation (RFA) and Microwave ablation (MWA) could reduce tumor burden and can stimulate an immune response, but it cannot maintain a lasting immune response. The alarming cytokine IL-33 is constitutively expressed by epithelial cells, endothelial cells, and fibroblasts, but is released during tissue injury to alert the immune system. The presence of ST2Tregs in TME may act as a barrier contributing to this phenomenon.

CX3CR1CD8 T cells: Key players in antitumor immunity.

CX3CR1 functions as the specific receptor for the chemokine CX3CL1, demonstrating expression across a broad spectrum of immune cells. This underscores its pivotal role in communication and response mechanisms within the immune system. Upon engagement with CX3CL1, CX3CR1 initiates a cascade of downstream signaling pathways that regulate various biological functions.

NUP37 promotes the proliferation and invasion of glioma cells through DNMT1-mediated methylation.

Nuclear regulation has potential in cancer therapy, with the nuclear pore complex (NPC) serving as a critical channel between the nucleus and cytoplasm, playing a role in regulating various biological processes and cancer. DNA methylation, an epigenetic modification mediated by DNA methyltransferases (DNMTs), influences gene expression and cell differentiation, and is crucial for the development and progression of tumor cells. Gliomas are the most common primary brain tumors, with glioblastoma being particularly aggressive, characterized by invasiveness, migration capability, and resistance to conventional treatments, resulting in poor prognosis.

Association of CD8TILs co-expressing granzyme A and interferon-γ with colon cancer cells in the tumor microenvironment.

CD8T cells secreting granzyme A (GZMA) can induce pyroptosis in tumor cells by effectively cleaving gasdermin B (GSDMB), which is stimulated by interferon-γ (IFN-γ). However, the interaction between GZMA-expressing CD8T cells and GSDMB-expressing tumor cells in colon cancer remains poorly understood. Our research employed multi-color immunohistochemistry (mIHC) staining and integrated clinical data to explore the spatial distribution and clinical relevance of GZMA- and IFN-γ-expressing CD8 tumor-infiltrating lymphocytes (TILs), as well as GSDMB-expressing CK cells, within the tumor microenvironment (TME) of human colon cancer samples.

Enhanced abscopal anti-tumor response via a triple combination of thermal ablation, IL-21, and PD-1 inhibition therapy.

Despite the success of immune checkpoint inhibitors (ICIs) in treating solid tumors, lots of patients remain unresponsive to this therapy. Microwave ablation (MWA) stimulates systemic adaptive immunity against tumor cells by releasing tumor antigens. Additionally, IL-21 has demonstrated importance in stimulating T-cell effector function.

Ferredoxin 1: a gatekeeper in halting lung adenocarcinoma progression through activation of the GPRIN2 signaling pathway.

Background: Lung adenocarcinoma (LUAD) is a highly lethal form of lung cancer. Despite advancements in treatments, managing LUAD is still challenging due to its aggressive behavior. Recent studies indicate that various molecular pathways, including the dysregulation of ferredoxin 1 (FDX1), play roles in LUAD progression.

Microwave ablation combined with PD-L1 blockade synergistically promotes Cxcl9-mediated antitumor immunity.

Although microwave ablation (MWA) is an important curative therapy in colorectal cancer liver metastasis, recurrence still occurs clinically. Our previous studies have shown that the expression of programmed cell death 1 ligand 1 (PD-L1) is upregulated following MWA, suggesting that MWA combined with anti-PD-L1 treatment can serve as a promising clinical therapeutic strategy against cancer. Using MWA-treated preclinical mice models, MWA combined with αPD-L1 treatment decreased tumor growth and prolonged overall survival (OS).

TIGIT Blockade Reshapes the Tumor Microenvironment Based on the Single-cell RNA-Sequencing Analysis.

Immune checkpoint blockade therapy is a pivotal approach in treating malignant tumors. TIGIT has emerged as a focal point of interest among the diverse targets for tumor immunotherapy. Nonetheless, there is still a lack of comprehensive understanding regarding the immune microenvironment alterations following TIGIT blockade treatment.

Precursor exhausted CD8T cells in colorectal cancer tissues associated with patient's survival and immunotherapy responsiveness.

Exhausted CD8T cells represent a distinct cellular lineage that emerges during both chronic infections and cancers. Recent studies have shown that persistent antigen exposure can drive the differentiation of precursor exhausted CD8T cells, termed T cells, which are characterized as TCF-1PD-1CD8T cells. Elevated T cell frequencies in the tumor microenvironment (TME) are associated with improved overall survival (OS) in cancer patients and heightened responsiveness to anti-PD-1 therapy.

Single-cell RNA sequencing indicates cordycepin remodels the tumor immune microenvironment to enhance TIGIT blockade's anti-tumor effect in colon cancer.

Both preclinical and clinical studies have extensively proven the effectiveness of TIGIT inhibitors in tumor immunotherapy. However, it has been discovered that the presence of CD226 on tumor-infiltrating lymphocytes is crucial for the effectiveness of both anti-TIGIT therapy alone and when combined with anti-PD-1 therapy for tumors. In our investigation, we observed that cordycepin therapy significantly augmented the expression of the Cd226 gene.

Cordycepin remodels the tumor microenvironment of colorectal cancer by down-regulating the expression of PD-L1.

Purpose: Colorectal cancer, as a common malignant tumor, poses a serious threat to human life. Cordycepin, derived from Cordyceps militaris extract, which was established as a capable inhibitor of tumor growth. Nevertheless, the precise antitumor mechanism of cordycepin in colorectal cancer cells remains elusive.

Single-cell RNA sequencing reveals the effects of anti-PD-L1 therapy on 3LL lung cancer model and its tumor microenvironment.

PD-L1 is expressed on antigen-presenting cells and tumor cells, thus allows tumor cells to escape immune surveillance. Moreover, targeting PD-L1 was also recommended and selected as important immune checkpoint inhibitors (ICIs) strategy in the treatment of advanced cancers due to the safety and activity. However, the detailed alteration of tumor microenvironment (TME) upon anti-PD-L1 therapy in lung cancer tumor model still needs to be resolved.

Cordycepin synergizes with CTLA-4 blockade to remodel the tumor microenvironment for enhanced cancer immunotherapy.

The strategy of using immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, leading to remarkable clinical outcomes. However, certain cancer types and patient demographics continue to face unique challenges. As a result, it is vital to investigate combination therapies that involve ICIs to boost therapeutic efficacy.

Synergism Between IL21 and Anti-PD-1 Combination Therapy is Underpinned by the Coordinated Reprogramming of the Immune Cellular Network in the Tumor Microenvironment.

Unlabelled: T cell-stimulating cytokines and immune checkpoint inhibitors (ICI) are an ideal combination for increasing response rates of cancer immunotherapy. However, the results of clinical trials have not been satisfying. It is important to understand the mechanism of synergy between these two therapeutic modalities.

CD226 identifies functional CD8T cells in the tumor microenvironment and predicts a better outcome for human gastric cancer.

It is well-known that CD226 serves as a critical activating receptor on various immune cells, such as lymphocytes and monocytes, and it is suggested to promote anti-tumor immunity in the tumor microenvironment (TME). Herein, we showed a crucial regulatory role of CD226 in CD8T cell-mediated anti-tumor response in TME of human gastric cancer (GC). Specifically, the increased CD226 expression in cancer tissues was significantly associated with better clinical outcomes in GC patients.

Mobilizing phospholipids on tumor plasma membrane implicates phosphatidylserine externalization blockade for cancer immunotherapy.

In "healthy" tumor cells, phosphatidylserine (PS) is predominately localized in the inner plasma membrane leaflet. During apoptosis, PS relocates to the outer leaflet. Herein, we established PS tumor models with tumor cells lacking PS flippase component CDC50A, constantly exposing PS but alive.

The Role of RNA mA Modification in Cancer Glycolytic Reprogramming.

As one of the main characteristics of neoplasia, metabolic reprogramming provides nutrition and energy to enhance cell proliferation and maintain environment homeostasis. Glycolysis is one of the most important components of cancer metabolism and the Warburg effect contributes to the competitive advantages of cancer cells in the threatened microenvironment. Studies show strong links between N-methyladenosine (mA) modification and metabolic recombination of cancer cells.