Tumor-infiltrating CCR2+ inflammatory monocytes counteract specific immunotherapy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1001913 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tumor development and progression is shaped by the tumor microenvironment (TME), a heterogeneous assembly of infiltrating and resident host cells, their secreted mediators and intercellular matrix. In this context, tumors are infiltrated by various immune cells with either pro-tumoral or anti-tumoral functions. Recently, we published our non-invasive immunization platform DIVA suitable as a therapeutic vaccination method, further optimized by repeated application (DIVA2). In our present work, we revealed the therapeutic effect of DIVA2 in an MC38 tumor model and specifically focused on the mechanisms induced in the TME after immunization. DIVA2 resulted in transient tumor control followed by an immune evasion phase within three weeks after the initial tumor inoculation. High-dimensional flow cytometry analysis and single-cell mRNA-sequencing of tumor-infiltrating leukocytes revealed cytotoxic CD8+ T cells as key players in the immune control phase. In the immune evasion phase, inflammatory CCR2+ PDL-1+ monocytes with immunosuppressive properties were recruited into the tumor leading to suppression of DIVA2-induced tumor-reactive T cells. Depletion of CCR2+ cells with specific antibodies resulted in prolonged survival revealing CCR2+ monocytes as important for tumor immune escape in the TME. In summary, the present work provides a platform for generating a strong antigen-specific primary and memory T cell immune response using the optimized transcutaneous immunization method DIVA2. This enables protection against tumors by therapeutic immune control of solid tumors and highlights the immunosuppressive influence of tumor infiltrating CCR2+ monocytes that need to be inactivated in addition for successful cancer immunotherapy.
| S-EPMC10577317 | biostudies-literature
Project description:We used Single-cell RNA-sequencing to analyze the composition of the tumor microenvironment of MC38mOVA tumors upon transcutaneous immunization with our immunization method DIVA.
2023-09-27 | GSE239384 | GEO
Project description:Monocytes have been categorized in three main subpopulations based on CD14 and CD16 surface expression. Classical monocytes are the most abundant subset in the blood. They express a CD14+CD16-CCR2+ phenotype, which confers on them the ability to migrate to inflammatory sites by quickly responding to CCL2 signaling. Here we identified and characterized the surge and expansion of a novel monocyte subset during SIV and HIV infection. They were undistinguishable from classical monocytes regarding CD14 and CD16 expression, but did not express surface CCR2. Transcriptome analysis of sorted cells confirmed that they represent a distinct subpopulation that expresses lower levels of inflammatory cytokines and activation markers than their CCR2+ counterparts. They exhibited impaired phagocytosis and deficient chemotaxis in response to CCL2 and CCL7, besides being refractory to SIV infection. We named these cells atypical CCR2- classical (ACC) monocytes, and believe they play an important role in AIDS pathogenesis, possibly reflecting an anti-inflammatory response against the extreme immune activation observed during SIV and HIV infection. Antiretroviral therapy caused this population to decline in both macaque and human subjects, suggesting that this atypical phenotype may be induced by viral replication. Expression profiling by NanoString nCounter gene expression system. Classical monocytes (CD14++CD16-) from six SIV-infected macaques (day 14 post inoculation) were sorted in two groups according to CCR2 expression.
2012-03-01 | E-GEOD-27559 | biostudies-arrayexpress
Project description:Monocytes have been categorized in three main subpopulations based on CD14 and CD16 surface expression. Classical monocytes are the most abundant subset in the blood. They express a CD14+CD16-CCR2+ phenotype, which confers on them the ability to migrate to inflammatory sites by quickly responding to CCL2 signaling. Here we identified and characterized the surge and expansion of a novel monocyte subset during SIV and HIV infection. They were undistinguishable from classical monocytes regarding CD14 and CD16 expression, but did not express surface CCR2. Transcriptome analysis of sorted cells confirmed that they represent a distinct subpopulation that expresses lower levels of inflammatory cytokines and activation markers than their CCR2+ counterparts. They exhibited impaired phagocytosis and deficient chemotaxis in response to CCL2 and CCL7, besides being refractory to SIV infection. We named these cells atypical CCR2- classical (ACC) monocytes, and believe they play an important role in AIDS pathogenesis, possibly reflecting an anti-inflammatory response against the extreme immune activation observed during SIV and HIV infection. Antiretroviral therapy caused this population to decline in both macaque and human subjects, suggesting that this atypical phenotype may be induced by viral replication. Expression profiling by NanoString nCounter gene expression system.
2012-03-01 | GSE27559 | GEO
Project description:The encapsulated yeast Cryptococcus neoformans can cause a fatal meningoencephalitis in immunocompromised patients. C. neoformans infection is acquired through the respiratory tract, but the cellular and molecular mechanisms of the pulmonary innate immune response are still not well defined. To investigate the response of CCR2+ inflammatory monocytes to C. neoformans, we compared the transcriptomes of CCR2+ inflammatory monocytes from the lungs of naïve versus infected mice.
2019-02-11 | GSE122765 | GEO
Project description:Gene-level transcriptome analysis of monocyte mRNA derived from mice that are genetically deficient of the Ccl2 gene or Ccr2 gene The CCL2/CCR2 chemokine axis is critical in monocytes mobilization and innate immunity. Although mice deficient in either gene manifest similar phenotype, such as reduced atherosclerosis, some biologic processes are disrupted in starkly different ways in these mice. We found in a Her2/neu driven mammary carcinoma model, the absence of Ccl2 inhibits tumor growth and prolongs survival, while genetic deletion of Ccr2 has the opposite effect. One of the postulated mechanisms is that Ccl2 and Ccr2 affect monocyte development in different manners. This experiment was designed to compare the whole transcriptome of monocytes that are deficient in either Ccl2 or Ccr2, with the hypothesis that differential development of these monocytes will manifest as differential gene expression profiles.
2016-10-21 | GSE88962 | GEO
Project description:Our study reports the CCR2 dependent functional specialization of monocytes into immature macrophages occurs within the TNF-TNFR2 activated vasculature and establishes a chemokine-based autocrine, feed-forward loop that may aplify the inflammation and renal injury.
2022-02-19 | GSE196930 | GEO
Project description:Our study reports that CCR2 dependent functional specialization of monocytes into immature macrophages occurs within the TNF-TNFR2 activated vasculature and establishes a chemokine-based autocrine, feed-forward loop that may aplify the inflammation and renal injury.
2022-02-21 | GSE196730 | GEO
Project description:Comparative analysis of FACS-sorted CCR2- and CCR2+ HSC in the steady state. CCR2+ HSC have fourfold higher proliferative rates than CCR2- HSC, are are biased towards the myeloid lineage and dominate the migratory HSC population. Comparison of pooled CCR2- and CCR2+ HSC (bone marrow from 20 mice pooled for each sample), three biological replicates each.
2015-05-01 | E-GEOD-53827 | biostudies-arrayexpress
Project description:In this experiment, dendritic cells and monocytes obtained from melanoma patients who underwent immunotherapy were stimulated with a maturation cocktail then either treated or not treated with denlieukin diftitox (DD; ONTAK) and then subjected to transcription profiling to investigate the effects of DD on the maturation and activation of dendritic cells and monocytes.
2013-09-04 | E-MTAB-977 | biostudies-arrayexpress