CXCL3 (C-X-C Motif Chemokine Ligand 3)

Emerging clinical and translational data indicate that disrupting this axis can sensitize MSS-CRC to ICIs: for example, Zanzalintinib combined with Atezolizumab reported survival benefit in the STELLAR-303 trial, and dual blockade of novel checkpoints with PD-(L)1 has been associated with enhanced immune activation in solid tumors. Targeting the MDSC-Treg axis therefore represents a promising strategy to overcome immunotherapy resistance in MSS/pMMR CRC.

This study systematically delineates a novel panel of early-detection biomarkers for CRC and identifies SB-225002 as a repurposed candidate therapeutic agent. The integrative strategy combining multi-cohort transcriptomic analysis, drug-repositioning platforms, molecular docking, and experimental validation offers a feasible framework for discovering clinically actionable biomarkers and small-molecule therapies for CRC.

Collectively, these findings indicate that as CRC advances, increased secretion of CXCL2 from malignant cells stimulates ACKR1 on ECs, thereby promoting tumor invasion and metastasis. This study provides a framework for stage-specific interventions, particularly for locally advanced CRC, by disrupting ACKR1 on ECs within TME to impede metastasis and improve clinical outcomes.

Our findings define a distinct NFKBIZ+ macrophage population that mechanistically links hypoxia, angiogenesis, and immune evasion to PD-1 blockade resistance. This work provides new insights into the cellular and molecular basis of immunotherapy failure in HCC and highlights potential targets for overcoming treatment resistance.

Therapeutically, microbiota modulation via diet, metformin, and probiotics shows promise. Gut microbiota lies at the nexus of T2DM and CRC, functioning as a modifiable mediator rather than a passive bystander. Future research should prioritize longitudinal, multi-omic, and intervention-driven studies to enable personalized prevention and treatment strategies.

Mechanistically, CXCL3 activated the PI3K/AKT/mTOR pathway by upregulating PI3K, p-PI3K, AKT, p-AKT, mTOR, and p-mTOR, while the mTOR inhibitor Torin 1 reversed these effects...In vivo, CXCL3 overexpression significantly promoted tumor growth in nude mice. These findings suggest CXCL3 facilitates liver cancer progression through tumor microenvironment modulation and PI3K/AKT/mTOR pathway activation.

FAM49B knockdown significantly inhibited MDK expression and disrupted ECM-receptor interactions. FAM49B promotes immunosuppressive TME formation by mediating TAM polarization via the MDK-NCL axis, suggesting the FAM49B-MDK-NCL pathway as a potential therapeutic target for CRC metastasis.

This study constructed the first CRGs-derived risk signature and revealed its role in tumor-immune-stromal crosstalk at single-cell resolution. The signature reflects tumor-immune interactions and therapeutic vulnerabilities, providing a basis for clinical risk stratification and personalized immunotherapy strategies.

Our multi-omics approach identified a malignant epithelial subset, C5, and a five-gene signature that stratifies gastric cancer prognosis and immune response. Functional assays showed that SRI knockdown impairs tumor cell growth, migration and invasion.

The study highlights the pivotal role of M1 macrophage-related DEGs in LUSC tumorigenesis. The newly identified 5 hub genes provide a highly accurate diagnostic tool for LUSC, offering potential improvements for both diagnostic and therapeutic strategies.

Notably, ZNF703, DDHD2, LSM1, and BAG4 are co-localized within the amplicons at the chromosome 8p11-p12 region, indicating a potential cooperative role in driving cancer initiation and progression. Collectively, these findings underscore the essential roles of ZNF703 in cancer development, patient prognosis, and the regulation of anti-tumor immunity, highlighting its potential as a biomarker for cancer detection and as a novel immunotherapeutic target.

Clinically, BFAR expression correlated with neutrophil infiltration and poor response to anti-PD-1 therapy, while its inhibition synergizes with immune checkpoint blockade in preclinical models. Our work unveils BFAR as a central orchestrator of neutrophil-driven immunosuppression and proposes targeting this axis to enhance immunotherapy efficacy in GC.