tumor microenvironment

Byaibio

The tumor microenvironment (TME) is the local pathophysiologic tumor niche that shapes progression, immune escape, and treatment response, acting as a major context for therapy rather than a single molecular target. It is often hypoxic and acidic, and one recent study showed that hydrogen release and hydroxide generation from calcium hydride can remodel this milieu to improve immunogenic transarterial chemoembolization (TACE) in hepatocellular carcinoma (PMID:41655909). Spatial organization of immune and stromal cells is central to TME function, with analyses such as spatial profiling and spahe infil used to decode infiltration patterns and predict immunotherapy response. The TME is implicated across multiple cancers, including non small cell lung cancer, gastric cancer, biliary tract cancer, breast cancer, ovarian cancer, esophageal cancer, PDAC, lymphoma, and hepatocellular carcinoma, and it is a key barrier to ADCs, oncolytic vaccinia virus, and other immunotherapies. Recent advances highlight mechanisms such as exosome-mediated crosstalk via b7 h3, macrophage metabolic reprogramming, lipid metabolism rewiring, neutrophil extracellular traps, tertiary lymphoid structures, and stromal stiffening that can be transiently softened by losartan to enhance delivery and immune activation. Overall, the literature emphasizes that remodeling the TME—through hydrogels, MOFs, dendritic-cell-derived exosomes, CRISPR-Cas12a-enabled network analysis, or metabolic and stromal interventions—can convert an immune-cold, therapy-resistant ecosystem into one more permissive to anti-tumor immunity.

Immunotherapy resistance and immune remodeling

  • The TME is a major determinant of immunotherapy response, with spatial immune-cell distribution used to explain heterogeneous outcomes in tumors (PMID:41971992).
  • In NSCLC, the TME is described as heterogeneous and linked to both progression and immunotherapy resistance; exosome-mediated crosstalk further promotes immune evasion and therapeutic resistance (PMID:41958218, PMID:41759799).
  • KRAS-mutated biliary tract cancer shows an immune-cold TME with reduced CD8+ T cells and APC infiltration plus impaired cell-cell interactions (PMID:41186264).
  • Post-radiation TME remodeling may still leave insufficient support for robust priming of new tumor-reactive responses, underscoring persistent immune suppression (PMID:41984232).
  • TME-targeted strategies include PSMD14-driven PD-L1 degradation, B7-H3-associated exosome biology, and platelet-induced VISTA expression in ovarian cancer (PMID:41981629, PMID:41964005, PMID:41841642).

Stromal, vascular, and delivery barriers

  • TME architecture can drive resistance to antibody-drug conjugates through stromal density, vascular heterogeneity, and immune modulation (PMID:41874465).
  • In PDAC, a high-stiffness stromal environment was transiently converted to a more compliant state by losartan, improving delivery and immune activation (PMID:41763269).
  • Dense tumor-associated microenvironments can physically limit access, but nanobodies were reported to penetrate these barriers (PMID:41936638).
  • Injectable smart hydrogels are being developed to locally remodel the TME and overcome multidrug resistance (PMID:41963941).
  • MOF-based drug delivery systems are also being explored to modulate the TME for immunotherapy (PMID:41643523).

Metabolic and myeloid-cell reprogramming

  • Lipid metabolism reprogramming reshapes the immune landscape of the TME by altering immune and stromal cell behavior to support tumor progression (PMID:41946907, PMID:41987491).
  • Tumor-associated macrophages are central regulators of the TME, with metabolic state changes influencing progression or regression and M2 polarization being a therapeutic target (PMID:41961489, PMID:41992232).
  • B-cell fatty acid metabolism has been proposed as a lever to enhance APC-like function within the TME and improve anti-tumor immunity (PMID:41984099).
  • Neutrophil extracellular traps act context-dependently within the TME to shape tumor biology and immune regulation (PMID:41987275).
  • Dendritic cell-derived exosomes are also described as regulators of the TME in anti-tumor activity (PMID:41954838).

Spatial profiling, molecular heterogeneity, and tumor initiation

  • Spatial multi-omics in gastric cancer reveals molecular disparities and cellular interactions within the TME that are not captured by bulk profiling (PMID:41892326).
  • Proteomic signatures in triple-negative breast cancer and other biomarker studies emphasize that TME interactions are regulated by protein-level context (PMID:41512917).
  • Esophageal cancer reviews highlight microenvironmental alterations as contributors to early tumor initiation and malignant progression (PMID:41986343).
  • Surgical resection and perioperative stress can rapidly remodel the immune and stromal compartments surrounding tumors (PMID:41880678).
  • CRISPR-Cas12a is being used as a tool to analyze molecular networks within the TME and broader oncology contexts (PMID:41500123).