CD58 defines regulatory macrophages within the tumor microenvironment
Ontology highlight
ABSTRACT:
SUBMITTER: Wu B
PROVIDER: S-EPMC11335740 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:High levels of ecto-5'-nucleotidase (CD73) have been implicated in immune suppression and tumor progression, and have also been observed in cancer patients who progress on anti-PD-1 immunotherapy. Although regulatory T cells can express CD73 and inhibit T cell responses via the production of adenosine, less is known about CD73 expression in other immune cell populations. We found that tumor-infiltrating NK cells upregulate CD73 expression and the frequency of these CD73-positive NK cells correlated with larger tumor size in breast cancer patients. In addition, the expression of multiple alternative immune checkpoint receptors including LAG-3, VISTA, PD-1, and PD-L1 was significantly higher in CD73-positive NK cells than in CD73-negative NK cells. Mechanistically, NK cells transport CD73 in intracellular vesicles to the cell surface and the extracellular space via actin polymerization-dependent exocytosis upon engagement of 4-1BBL on tumor cells. These CD73-positive NK cells undergo transcriptional reprogramming and upregulate IL-10 production via STAT3 transcriptional activity, suppressing CD4-positive T cell proliferation and IFN-γ production. Taken together, our results support the notion that tumors can hijack NK cells as a means to escape immunity and that CD73 expression defines an inducible population of NK cells with immunoregulatory properties within the tumor microenvironment.
| S-EPMC7269592 | biostudies-literature
Project description:For successful immunotherapy for cancer, it is important to understand the immunological status of tumor antigen-specific CD8+ T cells in the tumor microenvironment during tumor progression. In this study, we monitored the behavior of B16OVA-Luc cells in mice immunized with a model tumor antigen ovalbumin (OVA). Using bioluminescence imaging, we identified the time series of OVA-specific CD8+ T-cell responses during tumor progression: initial progression, immune control, and the escape phase. As a result of analyzing the status of tumor antigen-specific CD8+ cells in those 3 different phases, we found that the expression of NKG2D defines tumor-reacting effector CD8+ T cells. NKG2D may control the fate and TOX expression of tumor-reacting CD8+ T cells, considering that NKG2D blockade in OVA-vaccinated mice delayed the growth of the B16OVA-Luc2 tumor and increased the presence of tumor-infiltrating OVA-specific CD8+ T cells.
| S-EPMC8409295 | biostudies-literature
Project description:BackgroundThe role of androgens and other sex steroids is known to influence the prognosis and progression of prostate cancer through different disease states. While androgens are generally regarded as immunosuppressive and estrogens as inflammatory, the specific influence of sex steroids on the immune microenvironment of prostate tumors remains incompletely understood.Material and methodsIn this study, we evaluate the link between sex steroids and prostate cancer immune cells, particularly macrophages. Using in vitro and in vivo models, as well as ex vivo culture of patient prostate tissue, we evaluated the influence of androgen, estrogen, and progesterone on immune cells of the prostate microenvironment.ResultsIn vitro, we observed sex steroids induced indirect changes on prostate cancer cell proliferation via THP-1 derived macrophages, but no clear changes were induced using human monocyte derived macrophages. Comparing immunohistochemistry for immunosuppressive macrophage marker CD163 with concomitant circulating sex steroids from the same patients, we observed a correlation with higher dehydroepiandrosterone (DHEA)-sulfate and estrone-sulfate levels associated with higher prostate CD163 expression. Similar relationships between DHEA and CD163 levels were observed in ex vivo cultured prostate biopsies. Finally, in a murine prostate cancer model of long-term sex steroids we observed significant differences in tumor growth in mice implanted with estrogen and DHEA diffusion tubes.ConclusionsOur results highlight the complex influence of sex steroids on the immune cell composition of prostate tumors. Understanding this biology may help to further personalized therapy and improve patient outcomes.
| S-EPMC9077148 | biostudies-literature
Project description:IntroductionDespite advancements in the methods for prevention and early diagnosis of gastric cancer (GC), GC continues to be the fifth in incidence among major cancers and the third most common cause of cancer-related death. The therapeutic effects of surgery and drug treatment are still unsatisfied and show notable differences according to the tumor microenvironment (TME) of GC.MethodsThrough screening Pubmed, Embase, and Web of Science, we identified and summarized the content of recent studies that focus on the investigation of Helicobacter pylori (Hp) infection, regulatory T cells (Tregs), and tumor-associated macrophages (TAMs) in the TME of GC. Furthermore, we searched and outlined the clinical research progress of various targeted drugs in GC treatment including CTLA-4, PD-1\PD-L1, and VEGF/VEGFR.ResultsIn this review, the findings indicate that Hp infection causes local inflammation and leads to immunosuppressive environment. High Tregs infiltration in the TME of GC is associated with increased induction and recruitment; the exact function of infiltrated Tregs in GC was also affected by phenotypes and immunosuppressive molecules. TAMs promote the development and metastasis of tumors, the induction, recruitment, and function of TAMs in the TME of gastric cancer are also regulated by various factors.ConclusionDiscussing the distinct tumor immune microenvironment (TIME) of GC can deepen our understanding on the mechanism of cancer immune evasion, invasion, and metastasis, help us to reduce the incidence of GC, and guide the innovation of new therapeutic targets for GC eventually.
| S-EPMC10839124 | biostudies-literature
Project description:Macrophages are often prominently present in the tumor microenvironment, where distinct macrophage populations can differentially affect tumor progression. Although metabolism influences macrophage function, studies on the metabolic characteristics of ex vivo tumor-associated macrophage (TAM) subsets are rather limited. Using transcriptomic and metabolomic analyses, we now reveal that pro-inflammatory MHC-IIhi TAMs display a hampered TCA cycle, while reparative MHC-IIlo TAMs show a higher oxidative and glycolytic metabolism. Although both TAM subsets rapidly exchange lactate in high lactate conditions, only MHC-IIlo TAMs use lactate as an additional carbon source. Accordingly, lactate supports the oxidative metabolism in MHC-IIlo TAMs, while it decreased the metabolic activity of MHC-IIhi TAMs. Lactate subtly affected the transcriptome of MHC-IIlo TAMs, increased L-arginine metabolism and enhanced T-cell suppressive capacity of these TAMs. Overall, our data uncover the metabolic intricacies of distinct TAM subsets and identify lactate as a carbon source, and metabolic and functional regulator of TAMs.
2021-11-12 | GSE188549 | GEO
Project description:Tumor microenvironment consists of malignant and non-malignant cells. The interaction of these dynamic and different cells is responsible for tumor progression at different levels. The non-malignant cells in TME contain cells such as tumor-associated macrophages (TAMs), cancer associated fibroblasts, pericytes, adipocytes, T cells, B cells, myeloid-derived suppressor cells (MDSCs), tumor-associated neutrophils (TANs), dendritic cells (DCs) and Vascular endothelial cells. TAMs are abundant in most human and murine cancers and their presence are associated with poor prognosis. The major event in tumor microenvironment is macrophage polarization into tumor-suppressive M1 or tumor-promoting M2 types. Although much evidence suggests that TAMS are primarily M2-like macrophages, the mechanism responsible for polarization into M1 and M2 macrophages remain unclear. TAM contributes cancer cell motility, invasion, metastases and angiogenesis. The relationship between TAM and tumor cells lead to used them as a diagnostic marker, therapeutic target and prognosis of cancer. This review presents the origin, polarization, role of TAMs in inflammation, metastasis, immune evasion and angiogenesis as well as they can be used as therapeutic target in variety of cancer cells. It is obvious that additional substantial and preclinical research is needed to support the effectiveness and applicability of this new and promising strategy for cancer treatment.
| S-EPMC7539304 | biostudies-literature
Project description:ObjectiveTo generate an image-driven biomarker (Rad_score) to predict tumor-infiltrating regulatory T lymphocytes (Treg) in breast cancer (BC).MethodsOverall, 928 BC patients were enrolled from the Cancer Genome Atlas (TCGA) for survival analysis; MRI (n = 71 and n = 30 in the training and validation sets, respectively) from the Cancer Imaging Archive (TCIA) were retrieved and subjected to repeat least absolute shrinkage and selection operator for feature reduction. The radiomic scores (rad_score) for Treg infiltration estimation were calculated via support vector machine (SVM) and logistic regression (LR) algorithms, and validated on the remaining patients.ResultsLandmark analysis indicated Treg infiltration was a risk factor for BC patients in the first 5 years and after 10 years of diagnosis (p = 0.007 and 0.018, respectively). Altogether, 108 radiomic features were extracted from MRI images, 4 of which remained for model construction. Areas under curves (AUCs) of the SVM model were 0.744 (95% CI 0.622-0.867) and 0.733 (95% CI 0.535-0.931) for training and validation sets, respectively, while for the LR model, AUCs were 0.771 (95% CI 0.657-0.885) and 0.724 (95% CI 0.522-0.926). The calibration curves indicated good agreement between prediction and true value (p > 0.05), and DCA shows the high clinical utility of the radiomic model. Rad_score was significantly correlated with immune inhibitory genes like CTLA4 and PDCD1.ConclusionsHigh Treg infiltration is a risk factor for patients with BC. The Rad_score formulated on radiomic features is a novel tool to predict Treg abundance in the tumor microenvironment.
| S-EPMC10757114 | biostudies-literature
Project description:Tumor-associated macrophages (TAMs) are the most abundant population type of tumor-infiltrating immune cells found in the tumor microenvironment (TME), and are evolutionarily associated with microvessel density in tumor tissues. TAMs can be broadly divided into M1-like and M2-like TAMs, which demonstrate antitumor and pro-tumor activity in the TME, respectively. Studies have indicated that: i) The predominate presence of M2-like TAMs in the TME can result in tumor immunosuppression and chemoresistance; ii) the ratio of M1-like to M2-like TAMs in the TME is positively correlated with better long-term prognosis of patients with cancer; iii) epigenetic silencing, preventing the secretion of M1-like TAM-associated molecules, is an important immune evasion mechanism during tumor progression; and iv) the transformation from M2-like to M1-like TAMs following exposure to specific conditions can result in tumor regression. The present study discusses the molecular events underlying the recruitment of macrophages and their polarization into M1-like or M2-like TAMs, and their differential roles in angiogenesis, angiostasis, invasion, metastasis and immune activity in the TME. This insight may inform the improved design of TAM-targeted cancer immunotherapy. Some of these therapeutic strategies show promising effects; however, challenges remain.
| S-EPMC7500051 | biostudies-literature
Project description:Tumor-associated macrophages (TAM) have attracted attention as they can modulate key cancer-related activities, yet TAM represent a heterogenous group of cells that remain incompletely characterized. In growing tumors, TAM are often referred to as M2-like macrophages, which are cells that display immunosuppressive and tumorigenic functions and express the enzyme arginase 1 (Arg1). Methods: Here we combined high resolution intravital imaging with single cell RNA seq to uncover the topography and molecular profiles of immunosuppressive macrophages in mice. We further assessed how immunotherapeutic interventions impact these cells directly in vivo. Results: We show that: i) Arg1+ macrophages are more abundant in tumors compared to other organs; ii) there exist two morphologically distinct subsets of Arg1 TAM defined by previously unknown markers (Gbp2b, Bst1, Sgk1, Pmepa1, Ms4a7); iii) anti-Programmed Cell Death-1 (aPD-1) therapy decreases the number of Arg1+ TAM while increasing Arg1- TAM; iv) accordingly, pharmacological inhibition of arginase 1 does not synergize with aPD-1 therapy. Conclusion: Overall, this research shows how powerful complementary single cell analytical approaches can be used to improve our understanding of drug action in vivo.
| S-EPMC6299430 | biostudies-literature
Project description:Macrophages are metabolically heterogenous within the tumor microenvironment
| PRJNA779399 | ENA