Cell fusion with type 2 macrophage induce heterogeneity of melanoma cells that potentiate immunological escape from cytotoxic T lymphocytes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA866360 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20853209.fastq.gz | Fastqsanger.gz | |||
| SRR20853210.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 2 of 2 |
Similar Datasets
Project description:Evasion from immunity is a major obstacle for achievement of successful cancer immunotherapy. Hybrids derived from cell-cell fusion is a theory associated with tumor heterogeneity and progression by conferring novel properties to tumor cells, such as drug resistance or metastatic capacity; however, its impact on immune evasion remains still unknown. Here, we investigated the potency of hybrids in immune evasion using tumor-macrophage hybrids. Hybrids were established by co-culture of a melanoma cell line, A375 and type 2 macrophages. The hybrids showed higher migration ability and higher tumorigenicity than those of the parental melanoma cells. We found that the hybrids were less sensitive to T cell receptor (TCR) specific for NY-ESO-1 transduced T cells (TCR-T cells) than parental melanoma cells, although hybrids and parental melanoma cells showed equivalent NY-ESO-1 expression. An in vitro tumor heterogeneity model revealed that TCR-T cells preferentially killed parental cells than hybrids and the survival rate of hybrids were higher than that in parental cells indicating hybrids evade from killing by TCR-T cells efficiently. A single cell analysis data set revealed that a few macrophage cells expressed melanoma differentiation antigens including gp100, MART-1 and tyrosinase, indicating hybrids exist in primary melanoma, and number of potential hybrids were corelated with poorer response to immune checkpoint blockade. These results provide evidence that melanoma-macrophage fusion has a role in tumor heterogeneity and immune evasion.
2023-05-04 | GSE210578 | GEO
Project description:While some of the inflammatory mechanisms driving hepatocellular carcinoma (HCC) had been proposed, the regulators of anti-cancer immunity in HCC remain poorly understood. We found that IL-27 receptor (IL-27R) signaling promotes HCC development in vivo. High IL-27EBI3 or IL-27RA expression correlated with poor prognosis for patients with HCC. Loss of IL-27R suppressed HCC in vivo in two different models of hepatocarcinogenesis. Mechanistically, IL-27R signaling within the tumor microenvironment restrains the cytotoxicity of innate cytotoxic lymphocytes. IL-27R ablation enhanced the accumulation and activation, while depletion or functional impairment of innate cytotoxic cells abrogated the effect of IL-27R disruption. Pharmacological neutralization of IL-27 signaling increased infiltration of innate cytotoxic lymphocytes with upregulated cytotoxic molecules and reduced HCC development. Our data reveal an unexpected role of IL-27R signaling as an immunological checkpoint regulating innate cytotoxic lymphocytes and promoting HCC of different etiologies, thus indicating a therapeutic potential for IL-27 pathway blockade in HCC
2022-05-27 | GSE200040 | GEO
Project description:Cytotoxic T lymphocytes (CTL) kill malignant and infected cells via cytotoxic proteins such as granzyme B (GzmB) that are released into the immunological synapse in the form of ~110 nm supramolecular attack particles (SMAPs). However, it is not known where SMAPs are stored in the cell and how they are released. To address this, we utilized knock-in mice to label fusogenic cytotoxic granules with synaptobrevin2-mRFP. We identified two classes of fusion-competent granules, single core granules (SCG) and multi core granules (MCG), with different diameter, morphology, and protein composition. Functional analyses demonstrate that both classes of granules fuse with the plasma membrane at the IS. SCG fusion resulted in rapid dispersal of GzmB. MCG labelled with the SMAP marker thrombospondin-1 and their fusion events resulted in deposition of SMAPs. The CTL attack strategy thus includes SCG fusion to disperse immediately active cytotoxic proteins and parallel MCG fusion to deposit concentrated latent SMAPs onto the target.
2022-04-04 | PXD025055 | Pride
Project description:Highly Immunogenic Cancer Cells Require Activation of the WNT Pathway for Immunological Escape
| PRJNA753524 | ENA
Project description:Third dataset release from the Immunological Proteome Resource (ImmPRes). This dataset contains the study focussing on the effect of Hypoxia in Cytotoxic CD8+ Lymphocytes.
2021-11-03 | PXD020041 | Pride
Project description:Granules of cytotoxic T lymphocytes (CTL) are derived from the lysosomal compartment. Synaptotagmin7 (Syt7) appears to be the calcium sensor triggering fusion of lysosomes in fibroblasts. Syt7 has been proposed to control cytotoxic granule (CG) fusion in lymphocytes and mice lacking Syt7 have reduced ability to clear infections. However, fusion of CG persists in the absence of Syt7. To clarify the role of Syt7 in CTL function, we have examined the fusion of cytotoxic granules of CD8+ T-lymphocytes from Syt7 knock-out mice. We have recorded granule fusion in living CTL, using total internal reflection microscopy. Since Syt7 is considered a high affinity calcium-sensor specialized for fusion under low calcium conditions, we have compared cytotoxic granule fusion under low and high calcium conditions in the same CTL. There was no difference in latencies or numbers of fusion events per CTL under low-calcium conditions, indicating that Syt7 is not required for cytotoxic granule fusion. A deficit of fusion in Syt7 KO CTL was seen when a high-calcium solution was introduced. Expressing wild type Syt7 in Syt7 KO lymphocytes reversed this deficit, confirming its Syt7-dependence. Mutations of Syt7 which disrupt calcium binding to its C2A domain reduced the efficacy of this rescue. We counted the cytotoxic granules present at the plasma membrane to determine if the lack of fusion events in the Syt7 KO CTL was due to a lack of granules. In low calcium there were no differences in fusion events per CTL, and granule numbers were similar. In high calcium, granule number was similar though wild type CTL exhibited significantly more fusion than Syt7 KO CTL. The modest differences in granule counts do not account for the lack of fusion in high calcium in Syt7 KO CTL. In Syt7 KO CTL expressing wild type Syt7, delivery of cytotoxic granules to the plasma membrane was comparable to that of wild type CTL. Syt7 KO CTL expressing Syt7 with deficient calcium binding in the C2A domain had significantly less fusion and fewer CG at the plasma membrane. These results indicate that Syt7 is involved in trafficking of CG to the plasma membrane.
| S-EPMC7273742 | biostudies-literature
Project description:Viral mutational escape from CD8(+) cytotoxic T lymphocytes (CTLs) is typically considered to be a dichotomous process and uncommon during chronic HIV-1 infection. Ex vivo passaging of HIV-1 from persons with chronic infection, however, revealed the evolution of many fixed substitutions within and around CTL-targeted regions, with an associated increase in replicative capacity. This indicates an evolution of mutations during chronic HIV-1 infection that trade replicative fitness for incomplete evasion of CTLs, or "partial escape."
| S-EPMC3416319 | biostudies-literature
Project description:Second dataset release from the Immunological Proteome Resource (ImmPRes). This dataset contains both lymphoid and myeloid populations. The whole list is as follows: Bone marrow derived eosinophils, bone marrow derived mast cells, bone marrow derived macrophages, NK cells, TH2 cells, TH17 cells, Cytotoxic T cells cultured in IL15 and Naive CD8+ T cells extractred from the lymph nodes of C57BL/6J mice.
2020-07-02 | PXD020091 | Pride
Project description:Interleukin-27 signaling serves as an immunological checkpoint for innate cytotoxic cells to promote hepatocellular carcinoma
| PRJNA822782 | ENA
Project description:Effector cytotoxic T lymphocytes (CTLs) are critical for ridding the body of infected or cancerous cells. Recognition of an antigenic ligand by the CTL’s T cell receptor (TCR) triggers a signalling cascade that ultimately results in the targeted release of cytolytic granules and/or secretion of cytokines and chemokines to alert and recruit additional immune cells. These signalling cascades are capable of initiating transcription, translation, and cytoskeletal rearrangements. While previous work has demonstrated how translation and intracellular reorganisation contribute to CTL effector responses, the role of transcription is less well studied. To address this, we examined the impact of blocking transcription on the CTL proteome during TCR stimulation. These data demonstrated a strong transcriptional requirement for expression of cytokines and chemokines but not cytolytic molecules. Together with functional studies, these data reveal differential molecular control of the cell-cell communication and cytolytic functions of effector CTLs. CTLs exhibit complete and persistent priming for cytolytic activity prior to target cell encounter, but they require de novo transcription to recruit additional immune cells that amplify the response.
2023-10-16 | PXD034920 | Pride