Co-activating the intrinsic FcRγ/TLR4 signaling axis enhances the antitumor activity of NKG2D CAR-macrophages against prostate cancer.

The ZNF737-CXCL10 axis drives immune exclusion and resistance to anti-PD-1 therapy in bladder cancer.

In the tumor microenvironment (TME), "exhausted" CD8+ T cells are classified into progenitor (Tpex) and terminally exhausted (Ttex) populations. Tpex cells, critically regulated by zinc finger and BTB domain containing 27 (Zbtb27)/Bcl6 transcription factor, could be reinvigorated during immune checkpoint blockade (ICB) therapy, while Ttex cells, characterized by stronger proliferation and cytotoxicity, play an indispensable role in tumor control. However, the mechanisms governing the differentiation into Ttex and their function remain not well understood. In this study, we identified that Zbtb32, highly expressed in CD8+ Ttex subset, is crucial for CD8+ T cells within tumors. Zbtb32, regulated by CD28 signaling, promotes the differentiation of CD8+ T cells into Ttex subset, enhancing their cytotoxicity, proliferation, and anti-tumor capability. Importantly, we found a competitive DNA binding between Zbtb32 and Bcl6, especially in regulation of Id2 expression. Thus, our findings demonstrate the pivotal role of Zbtb32 in CD8+ T cell anti-tumor function, with implications in cancer immunotherapy.

GDF15 in the tumor microenvironment: A central mediator of cancer immunometabolism and therapeutic resistance.

Unmasking the role of tumor microenvironment in the advanced stage of cancer treatment to mitigate risks during chemotherapy.

Emerging roles of non-coding RNAs in the tumor microenvironment of pancreatic cancer: Focusing on current challenges and future directions.

High heterogeneity and an immunosuppressive tumor microenvironment (TME) are the core therapeutic bottlenecks of digestive system tumors. Current monotherapies face prominent limitations: immune checkpoint inhibitors (ICIs) yield low overall response rates as single agents, while long-term use of anti-angiogenic drugs (AADs) easily induces tumor resistance. To overcome these drawbacks, AAD-ICI combination therapy has become a research hotspot in this field, whose core synergy lies in coordinated TME modulation. AADs promote vascular normalization and reverse immunosuppressive TME to enhance intratumoral T lymphocyte infiltration, thereby laying a foundation for ICIs to exert anti-tumor effects and reactivating the endogenous anti-tumor immune response. Natural compounds have drawn extensive attention due to their regulatory value in TME remodeling and tumor combination therapy. However, there is still a lack of a comprehensive and systematic summary of their specific roles, molecular mechanisms and latest research progress in anti-angiogenic therapy, ICIs and their combination regimens for digestive system tumors. This deficiency impedes the further development of this research field. To fill this critical void, this review systematically elaborates the underlying mechanisms and clinical advances of AAD-ICI combination therapy for digestive system tumors. It also summarizes the regulatory functions and relevant research evidence of natural compounds in this therapeutic system, including those with dual regulatory effects. Additionally, the review analyzes existing challenges in basic research and clinical application, and outlines future research priorities. This work is expected to provide a valuable reference for the clinical translation and regimen optimization of precision immunotherapy for digestive system tumors.

Ectonucleotidases: Possible roles in the tumor microenvironment and influence on tumor progression in breast cancer.

Spatial and multi-omics transcriptomic dissects platinum resistance in lung adenocarcinoma: a five-gene predictive model with tumor microenvironment dynamics.

Shaping immunotherapy through the tumor microenvironment: Translational perspectives.

Protein palmitoylation and immune regulation in pancreatic ductal adenocarcinoma: Integrating insights from cross-cancer studies.

Engineering biohybrid nanozymes with near-infrared II light-enhanced catalysis for remodeling tumor microenvironment by disrupting energy metabolism.

Lung cancer remains a leading cause of global cancer mortality, with therapeutic efficacy significantly hampered by intrinsic and acquired therapy resistance. Solute carrier (SLC) and ATP-binding cassette (ABC) transporters have emerged as pivotal regulators orchestrating the transmembrane transport of diverse substrates to critically influence lung cancer progression and treatment response. This review systematically examines the pathophysiological roles of key transporters in lung cancer progression and therapeutic response, with a particular emphasis on their functions in mediating crosstalk within the tumor microenvironment (TME). It assesses the current knowledge in this field, elucidates the underlying molecular mechanisms, and highlights potential avenues for future research and clinical translation. SLC and ABC transporters critically contribute to the aggressiveness of lung cancer by orchestrating multiple facets of its malignant phenotype. This encompasses promoting cell proliferation, suppressing cell death, facilitating tumor invasion and metastasis, sustaining cancer stem cell (CSC) self-renewal, and modulating chemotherapy sensitivity and resistance. Furthermore, they mediate immunosuppression within the TME through dynamic crosstalk with resident stromal and immune cells. Thus, the substantial involvement of SLC and ABC transporters in lung cancer pathogenesis and therapeutic resistance definitively positions them as pivotal molecular vulnerabilities and actionable targets for developing novel therapeutic strategies to overcome drug resistance and improve clinical outcomes.

A hydrogen generator enhances immunogenic transarterial chemoembolization in hepatocellular carcinoma.

SNHG18 deficiency reprograms arginine metabolism to foster an immunosuppressive microenvironment in prostate cancer bone metastasis.

Therapeutic targeting of toll-like receptor pathways in tumor-associated macrophages.

Unraveling the glioblastoma (GBM) tumor microenvironment: future perspective on targeted immunotherapy.

Millimeter-scale, high-density three-dimensional constructs recapitulate hot and cold tumor microenvironment.

Ginsenosides remodel tumor immune microenvironment through metabolic reprogramming: Targets and mechanisms.

COL11A2 Methylation as a Biomarker for Radiosensitivity and Microenvironment Remodelling in Oral Squamous Cell Carcinoma.