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[Omnipresent Lactate: Normalization of the Tumor Microenvironment as a Prerequisite for Any Anticancer Therapy].

The history of research on lactate is quite interesting. At first, it was considered an unnecessary product of glycolysis, which humans use … blood vessels growing in them to reduce hypoxia and the lactate concentration. In addition, in the tumor microenvironment, where the concentration of lactate is dozens of times higher than normal, lactate acts as an immunosuppressant. In recent years, antitumor therapy has been reoriented from targeting tumor cells themselves to targeting immune cells (using "checkpoin …

The Therapeutic Potential of Targeting Tumor Microenvironment and Modulation of Immunotherapy in Gastrointestinal Cancer.

Immunotherapy, as a novel treatment approach for various disorders, including cancers, is designed to either stimulate or suppress the immun … cancer immunotherapy of GI cancers, chimeric antigen receptor T-cell (vehicle-T), modulators of the tumor microenvironment, and drug resistance mechanisms in immunotherapy as an effective treatment approach to GI cancers along with colon, pancreas, gastric, and esophageal cancers have been addressed. This review provides an overview of FDA-approved immunotherapy drugs a …

Role of the tumor microenvironment in chemotherapy resistance in ovarian cancer and targeted therapy.

Ovarian cancer is currently the gynaecological malignancy with the highest mortality rate, with a five-year survival rate of less than 50%. … ovarian cancer. There are many reasons for chemotherapy resistance in ovarian cancer patients, with tumor microenvironment emerging as a key focus. This "neighbor" has previously been regarded as a bystander during tumor initiation and growth. Through technological advances and deeper research, tumor microenvironment is now recognized as a critical active contributor to …

The role of the immune tumor microenvironment in shaping metastatic dissemination, dormancy, and outgrowth.

The tumor microenvironment (TME) is a dynamic and complex ecosystem composed of cancer cells and diverse non-malignant cell types, including immune cells, fibroblasts, and endothelial cells. Once viewed as passive bystanders, these host cells are now recognized as active participants in tumor progression, especially during metastasis. The TME varies by organ, cancer type, and disease stage, and shapes the trajectory of cancer progression. Among the immune cells in the TME, macrophages, neutrophils, and T cells play especially crucial and context-dependent roles - either promoting or inhibiting…

Spatial Landscape of Malignant Pleural and Peritoneal Mesothelioma Tumor Immune Microenvironments.

UNLABELLED: Immunotherapies have demonstrated limited clinical efficacy in malignant mesothelioma treatment. We conducted multiplex immunofluorescence analyses on tissue microarrays (n = 3) from patients with malignant pleural mesothelioma (MPM, n = 88) and malignant peritoneal mesothelioma (MPeM, n = 25). Our study aimed to elucidate spatial distributions of key immune cell populations and their association with lymphocyte activation gene 3 (LAG3), BRCA1-associated protein 1 (BAP1), neurofibromatosis type 2 (NF2), and methylthioadenosine phosphorylase (MTAP), with MTAP serving as a cyclin-dep

Multiple influence of immune cells in the bone metastatic cancer microenvironment on tumors.

Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high relapse rate. Immune and bone cells in situ constitute a unique immune microenvironment, which plays a crucial role in the context of bone metastasis. This review firstly focuses on lymphatic cells in bone metastatic cancer, including their function in tumor dissemination, invasion, growth and possible cytotoxicity-induced eradication. Subsequently, we examine myeloid cells, namely macrophages, myeloid-derived suppressor cells,

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… The tumor microenvironment (TME) is a composite of various components ( 5 ), including the immune microenvironment. Meanwhile, the bone plays an important role as an immune organ in the body. … Critical immunosuppressive effect of MDSC−derived exosomes in the tumor microenvironment. Oncol Rep. (2021) 45:1171–81. doi: 10.3892/or. 110. Danilin S, Merkel AR, Johnson JR, Johnson RW, Edwards JR, Sterling JA. …

A synergistic approach for modulating the tumor microenvironment to enhance nano-immunotherapy in sarcomas.

The lack of properly perfused blood vessels within tumors can significantly hinder the distribution of drugs, leading to reduced treatment e … eviates mechanical forces by decreasing 50 % collagen and hyaluronan levels and thus, reshaping the tumor microenvironment. Furthermore, the combined therapy normalizes the tumor vasculature by increasing two-fold the pericytes coverage. This combination not only improves six times tumor perfusion but also enhances drug delivery. As a result, blood vessel functionality …

The molecular landscape of T cell exhaustion in the tumor microenvironment and reinvigoration strategies.

Immunotherapy has emerged as a promising therapeutic approach for cancer treatment by harnessing the immune system to target cancer cells. However, the efficacy of immunotherapy is hindered by the tumor microenvironment (TME), comprising regulatory T cells (Tregs), macrophages, myeloid-derived suppressor cells (MDSCs), neutrophils, soluble factors (TGF-β, IL-35, IL-10), and hypoxia. These components interact with inhibitory receptors (IRs) on T cells, leading to alterations in T cell transcriptomes, epigenomes, and metabolism, ultimately resulting in T cell exhaustion and compromising the effe…

Comprehensive bioinformatics analysis of the role of VWF in the tumor microenvironment of malignant mesothelioma.

To explore the influence and effect of tumor microenvironment on the development of malignant mesothelioma using machine learning methods. 87 open cases were downloaded from the Cancer Genome Atlas database including transcriptome data, clinical data, and mutation data. The immune, stromal, and estimate scores were calculated for each case by using the ESTIMATE algorithm, and then the cases were grouped according to high and low stromal scores to predict all-cause survival in malignant mesothelioma cases. Their mutation data were analyzed to reveal the differences in mutated genes between the …

The Characteristics of Tumor Microenvironment Predict Survival and Response to Immunotherapy in Adrenocortical Carcinomas.

Increasing evidence confirms that tumor microenvironment (TME) can influence tumor progression and treatment, but TME is still understudied in adrenocortical carcinoma (ACC). In this study, we first scored TME using the xCell algorithm, then defined genes associated with TME, and then used consensus unsupervised clustering analysis to construct TME-related subtypes. Meanwhile, weighted gene co-expression network analysis was used to identify modules correlated with TME-related subtypes. Ultimately, the LASSO-Cox approach was used to establish a TME-related signature. The results showed that TM…

Extracellular vesicles in hematological malignancies: EV-dence for reshaping the tumoral microenvironment.

Following their discovery at the end of the 20th century, extracellular vesicles (EVs) ranging from 50-1,000 nm have proven to be paramount in the progression of many cancers, including hematological malignancies. EVs are a heterogeneous group of cell-derived membranous structures that include small EVs (commonly called exosomes) and large EVs (microparticles). They have been demonstrated to participate in multiple physiological and pathological processes by allowing exchange of biological material (including among others proteins, DNA and RNA) between cells. They are therefore a crucial way o

A review of spatial profiling technologies for characterizing the tumor microenvironment in immuno-oncology.

Interpreting the mechanisms and principles that govern gene activity and how these genes work according to -their cellular distribution in organisms has profound implications for cancer research. The latest technological advancements, such as imaging-based approaches and next-generation single-cell sequencing technologies, have established a platform for spatial transcriptomics to systematically quantify the expression of all or most genes in the entire tumor microenvironment and explore an array of disease milieus, particularly in tumors. Spatial profiling technologies permit the study of tra…

Immune Microenvironment and Immunotherapeutic Management in Virus-Associated Digestive System Tumors.

The development of cancer is a multifactorial phenomenon, while it constitutes a major global health problem. Viruses are an important facto … rectly with carcinogenesis by causing chronic inflammation in the infected organs. In addition, the tumor microenvironment contains various immune cells, endothelial cells, and fibroblasts, as well as several growth factors, cytokines, and other tumor-secreted molecules that play a key role in tumor growth, progression, and migration, while they are closely interrelated …

Characterization of the immune microenvironment in brain metastases from different solid tumors.

BACKGROUND: Brain metastases are one of the most common intracranial neoplasms. Increasing evidence have indicated that systemic immunotherapy may provide long-term benefits for brain metastases. Herein, we presented the results of an immune oncology panel RNA sequencing platform for patients with brain metastases from different primary sites. METHODS: We investigated 25 samples of human brain metastases from lung cancer (n = 12), breast cancer (n = 6), and colorectal cancer (n = 7). Besides, 13 paired samples of adjacent noncancerous brain tissue (10 from patients with lung cancer and 3 from

Influence of microenvironment and vascular anatomy on "metastatic" colonization potential of mammary tumors.

This communication reports experiments demonstrating that some sites in which tumor cells lodge reproducibly fail to support secondary colony formation by a particular tumor, even though cells from the same tumor are already proven to have high colonization potential in other organs. The effect is not an expression of nonspecific hostility to tumor growth, since cells from certain other tumors readily colonize the same site. Cell suspensions obtained by disaggregation of a series of naturally occurring murine mammary tumors were each inoculated by four different routes into separate batches of

Impact of aging on the tumor microenvironment in oral cancer: Mechanisms and therapeutic perspectives.

Oral cancer is a significant health problem worldwide, with particularly great impacts on elderly people. The aging process has a major impact on the tumor microenvironment (TME), affecting tumor initiation, progression, and the response to therapy. The present review summarizes the existing evidence regarding the effects of aging on the TME in oral cancer, the progression of oral diseases, and the implications for therapy. Studies were retrieved by conducting a structured literature search in the PubMed and MEDLINE databases from January 2010 to January 2025. Various age-related events such a…

In Silico Analysis of the Dual Role of Tumor Microenvironment on Colon Cancer Subtypes.

BACKGROUND: Colon cancer is a highly heterogeneous disease, marked by substantial intra- and inter-tumor variability. Investigating transcri … scriptomic profiles. Additionally, to investigate the implicated factors, such as mutations and the tumor microenvironment (TME), that affect colon cancer progression and their implications for therapy. METHODS: RNA-sequencing data from The Cancer Genome Atlas Colon Cancer (TCGA-COAD) cohort were obtained from the UCSC Xena database, including 47 early and 39 late-stag …

Systemically inducing trained immunity overcomes solid tumors' immunosuppressive microenvironment.

Hematopoietic bone marrow progenitors are increasingly implicated as an origin of immunosuppression in cancer. We have previously shown that trained immunity induction using nanomedicine potentiates checkpoint blockade therapy. Here, we studied how this approach's induction of trained immunity systemically overcomes the immunosuppressive tumor microenvironment. We found changes in the tumor microenvironment to mirror functional changes in the hematopoietic system in a melanoma mouse model. Single cell sequencing methods disclosed a shift in the tumor-associated macrophage population from immun…

Quantification of the tumor microenvironment and prognostic analysis in colorectal cancer based on CAMuTILS.

The complex spatial organization of the tumor microenvironment (TME) plays a critical role in colorectal cancer progression, yet its quantitative characterization from histopathological images remains challenging and often relies on subjective pathological assessment. In this study, we develop a CAMuTILS-based TME scoring framework for quantitative analysis and prognostic evaluation in colorectal cancer. First, we propose CAMuTILS, a panoptic segmentation network for histopathological images. The model adopts a dual-branch U-shaped architecture to simultaneously segment tissue regions and cell…

Modulation of the tumor microenvironment by incretins and glucagon: Metabolic and immune mechanisms (Review).

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and therapies targeting glucose-dependent insulinotropic polypeptide (GIP) have demonstrated efficacy in the treatment of type 2 diabetes (T2D) and obesity. GLP-1 and GIP are collectively referred to as incretins. The strong epidemiological link between T2D/obesity and cancer risk suggests that GLP-1 and GIP may serve a substantial role in tumor metabolism. The effects of incretin hormones and the counter-regulatory hormone glucagon (GCG) on tumor biology may have important implications for understanding tumor microenvironmental regulation a…