The tumor immune microenvironment is the central immune context of tumors, and its primary function is to shape how cancers respond to therapy by being dynamically remodeled by treatment. Therapy-induced changes in this microenvironment can alter immunotherapy responsiveness, and recent work highlights its use as a central biological system for studying multi-omics, single-cell sequencing, and spatial transcriptomics. It is implicated across multiple disease areas, including esophageal squamous cell carcinoma, triple-negative breast cancer, lung squamous cell carcinoma, colorectal cancer with POLE/POLD1 deficiency, and multiple cancers linked to DLEC1 silencing. Mechanistically, the TIME can be immunosuppressive, as in NET-positive tumor-associated neutrophils in TNBC, or reprogrammed toward antitumor immunity by nanoplatforms and microbial communities. Recent studies also show that extreme neoantigen density in POLE/POLD1-deficient colorectal cancer reshapes the TIME, while SSX1 and TRIM58 expression can stratify lung squamous cell carcinoma by immune microenvironment features and potential immunotherapy responsiveness. Overall, the literature supports the TIME as a heterogeneous, therapy-sensitive system that is both a biomarker and a mechanistic driver of clinical benefit and immunotherapy prognosis.
Therapy response and remodeling
- Therapy-induced remodeling of the tumor immune microenvironment is a major mechanism influencing immunotherapy responsiveness and is being dissected with multi-omics, single-cell sequencing, and spatial transcriptomics. (PMID:41813658)
- The TIME is described as a central biological context affected by therapeutic interventions, emphasizing its role in treatment response. (PMID:41813658)
- Advanced nanoplatforms can reprogram the microenvironment to support antitumor immunity in urinary system tumors. (PMID:41947122)
- Therapy-driven alterations in the TIME are a focus of mechanistic and translational studies aimed at improving immunotherapy outcomes. (PMID:41813658)
Immunosuppression and immune modulation
- In TNBC, NET-positive tumor-associated neutrophils contribute to an immunosuppressive tumor microenvironment with prognostic value. (PMID:41671779)
- Microbial communities modulate the tumor immune microenvironment to influence antitumor immunity and immune suppression. (PMID:41963781)
- The microenvironment can be reprogrammed by nanomedicine-based strategies to shift immune balance toward antitumor activity. (PMID:41947122)
- Multi-omics analysis links NET+ TAN biology to immunosuppressive TME features and malignant clinical characteristics. (PMID:41671779)
Biomarkers, stratification, and prognosis
- In ESCC, heterogeneity of the esophageal squamous cell carcinoma immune microenvironment is a key determinant of clinical benefit, tumor behavior, and immunotherapy prognosis. (PMID:41814475)
- SSX1 and TRIM58 expression stratify lung squamous cell carcinoma by TIME characteristics and inform potential immunotherapy responsiveness. (PMID:42030005)
- Epigenetic silencing of DLEC1 correlates with the tumor immune microenvironment and predicts immunotherapy prognosis in multiple cancers. (PMID:42002658)
- The TIME is used as a prognostic and predictive framework across cancers, including immunopredictive modeling in ESCC. (PMID:41814475)
Genomic and neoantigen-driven remodeling
- POLE/POLD1 proofreading deficiency reshapes the tumor immune microenvironment through extreme neoantigen density in colorectal cancer. (PMID:42017297)
- This neoantigen-rich state is linked to immune checkpoint inhibitor biology and clinical practice in POLE/POLD1-deficient CRC. (PMID:42017297)
- DLEC1 epigenetic silencing is associated with TIME features across multiple cancers, suggesting a broader immune-regulatory role. (PMID:42002658)
- Genomic context can therefore reprogram immune composition and influence immunotherapy sensitivity. (PMID:42017297)