Tumor microenvironment
The tumor microenvironment (TME) refers to the complex, dynamic ecosystem surrounding and infiltrating a malignant tumor, comprising not only cancer cells but also a heterogeneous mixture of stromal cells, immune cells, extracellular matrix components, blood vessels, and soluble signaling molecules.
The tumor microenvironment (TME) refers to the complex, dynamic ecosystem surrounding and infiltrating a malignant tumor, comprising not only cancer cells but also a heterogeneous mixture of stromal cells, immune cells, extracellular matrix components, blood vessels, and soluble signaling molecules. Far from being a passive bystander, the TME actively participates in regulating tumor initiation, progression, immune evasion, metastasis, and therapeutic resistance. Key cellular constituents include tumor-associated macrophages (TAMs), cytotoxic T cells, regulatory T cells, dendritic cells, natural killer cell, B cells, cancer-associated fibroblasts, myeloid-derived suppressor cells (MDSCs), and neutrophils, all of which engage in intricate bidirectional crosstalk with neoplastic cells through cytokines, chemokines, metabolites, and exosomes. The physical and chemical characteristics of the TME — including hypoxia, acidosis, elevated reactive oxygen species (ROS), and immunosuppressive metabolite gradients — collectively shape a milieu that frequently supports tumor survival and shields cancer cells from immune surveillance.
A defining hallmark of many TMEs is their immunosuppressive character, which drives resistance to both conventional therapies and modern immunotherapy. This immunosuppression is orchestrated through multiple overlapping mechanisms: the polarization of macrophages toward an M2-like, pro-tumorigenic phenotype; the accumulation of regulatory T cells and MDSCs; the co-expression of immune checkpoint molecules such as Programmed cell death 1 (PD-1), CD274 molecule, LAG-3, TIGIT, VISTA, and B7-H3 (CD276); and the secretion of immunosuppressive cytokines such as transforming growth factor-beta (TGF-β) and IL-10. Understanding and therapeutically reprogramming the TME has emerged as one of the central challenges and opportunities in contemporary oncology, driving research across virtually every cancer type and treatment modality.
Where the papers sit
13 papers from the last 6 months study tumor microenvironment directly · updated from PubMed 8 Oct 2026
Study type 2 clinical trials · 3 human data · 6 preclinical · 2 unclassified
Themes 3 themes
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Immune Remodeling for Cancer Therapy
Tumor immunity is being treated as a remodeling problem rather than a fixed barrier to immunotherapy. Tumor-derived antioxidants suppress T-cell activity, while PI3Kγ inhibition, membrane-active peptides, cGAS-STING activation and HIFU aim to restore immune function. Physical activity is being linked to greater immune-cell infiltration in non-metastatic colon cancer. The approaches remain early and varied, with macrophage and CD8-positive T-cell responses as recurring endpoints.
5 papers · 38.5%
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Lung Cancer Immunotherapy
Lung adenocarcinoma treatment is moving toward combination immunotherapy that engineers the tumor microenvironment and addresses resistance. Extracellular-vesicle photoimmunotherapy, inhaled nitric oxide and mRNA-encoded OX40L, IL-23 and IL-36γ are being paired with checkpoint blockade or chemotherapy. Galactose metabolic reprogramming is a recurrent target in KRAS-mutant tumors. LOAd703 extends this strategy into early clinical testing, while durability and patient selection remain unresolved.
5 papers · 38.5%
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Cancer Evolution and Treatment Resistance
Multi-omic profiling is moving toward integrated maps of cancer evolution, prognosis and therapy resistance. Bulk and single-cell transcriptomes repeatedly identify tumor ecosystems, immune features and candidate hub genes. EcDNA, protein ubiquitination, androgen-receptor signaling and 3D chromatin architecture emerge as distinct routes shaping disease progression across osteosarcoma, neuroendocrine prostate cancer and LUAD. Machine-learning signatures are prominent, but clinical validation and mechanistic testing remain open.
3 papers · 23.1%
Papers
The 13 papers from the last 6 months that study tumor microenvironment directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
Immune Remodeling for Cancer Therapy (5)
- Association of objectively assessed physical activity with immune cell infiltration of the tumor microenvironment in non-metastatic colon cancer. International journal of colorectal disease · 10 Sept 2026 PMID 42720727
- Tumor-derived antioxidants suppress immunity by depriving T cells of reactive oxygen species. Science (New York, N.Y.) · 3 Sept 2026 PMID 42691162
- Development of a mobile high-intensity focused ultrasound platform for preclinical tumor microenvironment modulation in a pancreatic ductal adenocarcinoma mouse model. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group · 18 Aug 2026 PMID 42609051
- pH-Responsive liposomes co-delivering a membrane-active peptide and the PI3Kγ inhibitor to reconstruct the tumor microenvironment for enhanced antitumor immunotherapy. Biomaterials science · 17 Aug 2026 PMID 42605855
- "Yong" syndrome-cGAS-STING axis: a TCM syndrome-based hypothesis for overcoming primary anti-PD-1 resistance in gastric cancer. Journal for immunotherapy of cancer · 4 Aug 2026 PMID 42552062
Lung Cancer Immunotherapy (5)
- An Inhalable Hybrid Nitric Oxide Nanogenerator for Lung Adenocarcinoma Treatment via Bioorthogonal-Activated Gas-Immunotherapy. Journal of the American Chemical Society · 9 Sept 2026 PMID 42714559
- Targeting galactose metabolic reprogramming overcomes immunotherapy resistance in KRAS-mutant lung adenocarcinoma: Integrative multi-omics and machine learning approaches. Translational oncology · 6 Jul 2026 PMID 42407377
- Targeted extracellular vesicle-photoimmunotherapy remodels stromal-immune microenvironment to boost chemo-immunotherapy in preclinical models. Cell reports. Medicine · 3 Jun 2026 PMID 42235518
- Lipid Nanoparticle-Encapsulated mRNA-2752 Encoding Human OX40L, IL-23, and IL-36γ plus Durvalumab Induces an Immunostimulatory Effect within the Tumor Microenvironment in Patients with Advanced Solid Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research · 18 May 2026 PMID 42149124
- Tumor Microenvironment Gene Engineering with LOAd703 in Patients with Solid Malignancies: LOKON002 Phase I/IIb Clinical Trial. Clinical cancer research : an official journal of the American Association for Cancer Research · 29 Apr 2026 PMID 42053989
Cancer Evolution and Treatment Resistance (3)
- Ubiquitination-anchored signature defines neuroendocrine prostate cancer: hub genes and single-cell ecosystem insights from integrated bioinformatics analysis of public transcriptomic datasets. The aging male : the official journal of the International Society for the Study of the Aging Male · 6 Jun 2026 PMID 42249833
- 3D chromatin architecture-related genes orchestrate LUAD evolution and therapy resistance: insights from integrative machine learning and spatial single-cell mapping. Functional & integrative genomics · 4 Jun 2026 PMID 42240917
- Integrating single-cell and bulk transcriptomes to reveal prognostic and immunological features of ecDNA-related genes in osteosarcoma. Cancer immunology, immunotherapy : CII · 28 Apr 2026 PMID 42047819
By study type
Clinical trials (2)
- Lipid Nanoparticle-Encapsulated mRNA-2752 Encoding Human OX40L, IL-23, and IL-36γ plus Durvalumab Induces an Immunostimulatory Effect within the Tumor Microenvironment in Patients with Advanced Solid Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research · 18 May 2026 PMID 42149124
- Tumor Microenvironment Gene Engineering with LOAd703 in Patients with Solid Malignancies: LOKON002 Phase I/IIb Clinical Trial. Clinical cancer research : an official journal of the American Association for Cancer Research · 29 Apr 2026 PMID 42053989
Human data, design not indexed (3)
- Association of objectively assessed physical activity with immune cell infiltration of the tumor microenvironment in non-metastatic colon cancer. International journal of colorectal disease · 10 Sept 2026 PMID 42720727
- "Yong" syndrome-cGAS-STING axis: a TCM syndrome-based hypothesis for overcoming primary anti-PD-1 resistance in gastric cancer. Journal for immunotherapy of cancer · 4 Aug 2026 PMID 42552062
- 3D chromatin architecture-related genes orchestrate LUAD evolution and therapy resistance: insights from integrative machine learning and spatial single-cell mapping. Functional & integrative genomics · 4 Jun 2026 PMID 42240917
Preclinical: animal, cell and lab studies (6)
- An Inhalable Hybrid Nitric Oxide Nanogenerator for Lung Adenocarcinoma Treatment via Bioorthogonal-Activated Gas-Immunotherapy. Journal of the American Chemical Society · 9 Sept 2026 PMID 42714559
- Tumor-derived antioxidants suppress immunity by depriving T cells of reactive oxygen species. Science (New York, N.Y.) · 3 Sept 2026 PMID 42691162
- Development of a mobile high-intensity focused ultrasound platform for preclinical tumor microenvironment modulation in a pancreatic ductal adenocarcinoma mouse model. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group · 18 Aug 2026 PMID 42609051
- pH-Responsive liposomes co-delivering a membrane-active peptide and the PI3Kγ inhibitor to reconstruct the tumor microenvironment for enhanced antitumor immunotherapy. Biomaterials science · 17 Aug 2026 PMID 42605855
- Targeted extracellular vesicle-photoimmunotherapy remodels stromal-immune microenvironment to boost chemo-immunotherapy in preclinical models. Cell reports. Medicine · 3 Jun 2026 PMID 42235518
- Integrating single-cell and bulk transcriptomes to reveal prognostic and immunological features of ecDNA-related genes in osteosarcoma. Cancer immunology, immunotherapy : CII · 28 Apr 2026 PMID 42047819
Unclassified: not yet indexed with MeSH (2)
- Targeting galactose metabolic reprogramming overcomes immunotherapy resistance in KRAS-mutant lung adenocarcinoma: Integrative multi-omics and machine learning approaches. Translational oncology · 6 Jul 2026 PMID 42407377
- Ubiquitination-anchored signature defines neuroendocrine prostate cancer: hub genes and single-cell ecosystem insights from integrated bioinformatics analysis of public transcriptomic datasets. The aging male : the official journal of the International Society for the Study of the Aging Male · 6 Jun 2026 PMID 42249833
Written from 13 PubMed abstracts, each one listed by PMID above. Published: 2026-06-14. Last written: 2026-09-12 by GPT. Drafted by language models from published abstracts; not medical advice.