Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA147169 | ENA |
REPOSITORIES: ENA
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Project description:We have previously shown that within tumors, recombinant interleukin-2 (rIL-2, Aldesleukin) consistently activates tumor-associated macrophages and up-regulates interferon stimulated genes (ISGs) while inducing minimal migration, activation or proliferation of T-cells. These effects are independent of tumor response to treatment. Here, we prospectively evaluated transcriptional alterations induced by rIL-2 in peripheral blood mononuclear cells (PBMCs) and within melanoma metastases by serially comparing pre- to post-treatment samples in 13 patients. We also compared transcriptional differences among lesions displaying different responsiveness to therapy, focusing on 2 lesions decreasing in size and 2 remaining stable (responding lesions) compared to non-responding ones. As previously described, the effects of rIL-2 were dramatic within PBMC, while effects within the tumor microenvironment were lesion-specific and limited. However, distinct signatures specific to response could be observed in responding lesions pre-treatment that were amplified following rIL-2 administration. These signatures match the functional profile observed in other human or experimental models in which immune-mediated tissue-specific destruction (TSD) occurs underlying a common pathways leading to rejection. Moreover, the signatures observed in pre-treatment lesions were qualitatively similar to those associated with TSD underlining a determinism to immune responsiveness that depends upon the genetic background of the host or the intrinsic genetic makeup of individual tumors. This is the first prospectively collected insight on global transcriptional events occurring during high-dose rIL-2 therapy in melanoma metastases responding to treatment. Evaluated transcriptional alterations induced by rIL-2 in peripheral blood mononuclear cells (PBMCs) (n=34) and within melanoma metastases (n=30) by serially comparing pre- (n=34) to post-treatment (n=30) samples in 13 patients.
2012-10-01 | E-GEOD-32611 | biostudies-arrayexpress
Project description:We have previously shown that within tumors, recombinant interleukin-2 (rIL-2, Aldesleukin) consistently activates tumor-associated macrophages and up-regulates interferon stimulated genes (ISGs) while inducing minimal migration, activation or proliferation of T-cells. These effects are independent of tumor response to treatment. Here, we prospectively evaluated transcriptional alterations induced by rIL-2 in peripheral blood mononuclear cells (PBMCs) and within melanoma metastases by serially comparing pre- to post-treatment samples in 13 patients. We also compared transcriptional differences among lesions displaying different responsiveness to therapy, focusing on 2 lesions decreasing in size and 2 remaining stable (responding lesions) compared to non-responding ones. As previously described, the effects of rIL-2 were dramatic within PBMC, while effects within the tumor microenvironment were lesion-specific and limited. However, distinct signatures specific to response could be observed in responding lesions pre-treatment that were amplified following rIL-2 administration. These signatures match the functional profile observed in other human or experimental models in which immune-mediated tissue-specific destruction (TSD) occurs underlying a common pathways leading to rejection. Moreover, the signatures observed in pre-treatment lesions were qualitatively similar to those associated with TSD underlining a determinism to immune responsiveness that depends upon the genetic background of the host or the intrinsic genetic makeup of individual tumors. This is the first prospectively collected insight on global transcriptional events occurring during high-dose rIL-2 therapy in melanoma metastases responding to treatment.
2012-10-01 | GSE32611 | GEO
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2026-02-23 | E-MTAB-16710 | biostudies-arrayexpress
Project description:Homeostatic programs maintain equilibrium between immune protection, and selftolerance. Such mechanisms impact autoimmunity and tumor formation, respectively. How tissue homeostasis is maintained, and impacts tumor surveillance is unknown. Here we identify that mononuclear phagocytes share conserved programming during homeostatic differentiation, and entry into tissue. IFNγ is necessary and sufficient to induce these transcripts, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify metastatic melanoma survival. Single-cell RNA-sequencing reveals enrichment of these modules in monocytes and DCs in human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2), a highly conserved transcript in this program is induced by IFNγ, and expressed in mononuclear phagocytes infiltrating primary melanoma. SOCS2 limits DC adaptive anti-tumoral immunity and T cell priming in vivo, indicating a critical regulatory role. Our findings link homeostasis in peripheral tissue to anti-tumoral immunity and escape, revealing coopting of tissue-specific immune development in the tumor microenvironment.
2017-06-27 | GSE100050 | GEO
Project description:The imbalance of cellular homeostasis during oncogenesis together with the high heterogeneity of tumor-associated stromal cells have a marked effect on the repertoire of the proteins secreted by malignant cells (the secretome). Hence, the study of tumoral secretomes provides insights for understanding the cross-talk between cells within the tumor microenvironment as well as the key effectors for the establishment of the pre-metastatic niche in distant tumor sites. In this context, we performed a proteomic analysis of the secretomes derived from four cell lines: (i) a paired set of fibroblasts - Hs 895. T, a cell line obtained from a lung node metastatic site from a patient who had melanoma and Hs 895.Sk, a skin fibroblast cell line (derived from the same patient); (ii) two malignant metastatic melanoma cell lines - A375, a malignant melanoma cell line from primary source and SH-4, a cell line derived from pleural effusion of a patient with metastatic melanoma. Clustering of expression profiles together with functional enrichment revealed patterns that mirrored each cell type (skin fibroblasts, cancer-associated fibroblasts and metastatic cells). These patterns might be the result of cell-specific protein expression programs and may serve as basis for further proteomic analysis of melanoma cell lines secretomes.
2018-01-02 | PXD007265 | Pride
Project description:Homeostatic programs maintain equilibrium between immune protection, and selftolerance. Such mechanisms impact autoimmunity and tumor formation, respectively. How tissue homeostasis is maintained, and impacts tumor surveillance is unknown. Here we identify that mononuclear phagocytes share conserved programming during homeostatic differentiation, and entry into tissue. IFNγ is necessary and sufficient to induce these transcripts, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify metastatic melanoma survival. Single-cell RNA-sequencing reveals enrichment of these modules in monocytes and DCs in human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2), a highly conserved transcript in this program is induced by IFNγ, and expressed in mononuclear phagocytes infiltrating primary melanoma. SOCS2 limits DC adaptive anti-tumoral immunity and T cell priming in vivo, indicating a critical regulatory role. Our findings link homeostasis in peripheral tissue to anti-tumoral immunity and escape, revealing coopting of tissue-specific immune development in the tumor microenvironment. The raw FASTQ sequence files are being deposited in dbGAP.
2017-06-29 | GSE100337 | GEO
Project description:The advent of immune checkpoint blockade has improved patient outcomes, providing durable disease control by reversing localized tumor-mediated immune-suppression and promoting anti-tumor immunity. Despite successes in melanoma and lung cancer, these therapies have largely failed in pancreatic ductal adenocarcinoma (PDA); a ‘cold’ tumor with the highest mortality rate among all major cancers. PDA is uniquely characterized by multiple intra-pancreatic tumor- and stroma-induced mechanisms of immune-suppression, and there remains a great need to explore creative approaches to improve anti-tumor immune responses in this disease. Herein, we show routine aerobic exercise provides tumor-protective benefits in murine PDA through modulation of both systemic and intra-tumoral immunity. Reversing immune-suppressive properties of both myeloid and T cell populations, we found the anti-tumor benefits of exercise require CD8 T cell activation and expansion in the tumor. Specifically, we report the sub-population of IL15Ra+ CD8 T cells is required for exercise-induced tumor protection and anti-tumor immunity, both of which are abrogated in the context IL-15 blockade. We further show that exercise-induced increases in intra-tumoral T cells are governed by adrenergic signaling and S1P-gradient dependent lymphocyte migration. Finally, we found that combination with aerobic exercise sensitizes pancreatic tumors to anti-PD-1 therapy. Overall, our work highlights the unique mechanisms governing exercise-induced tumor protection in PDA, and uncovers the importance of the interplay between systemic and intra-tumoral immunity to develop innovative strategies to reverse immune-suppression in this devastating disease.
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Project description:Our study provides a comprehensive multiomics overview of each patient’s tumor, revealing tumor cell types, proteomics, and transcriptomic changes related to melanoma brain metastasis (MBM). Here, we have applied the HiRIEF pre-fractionation and tandem mass tags (TMT)-16plex based peptide quantification to generate proteomes of multiple neighboring regions within each MBM tumor tissue. PCA and Hierarchical clustering analysis illustrated higher inter-tumoral heterogeneity than intra-tumoral heterogeneity of MBM at the protein levels, as lesions from the same patients are grouped into a single cluster. The treatment-naive patient (P3) exhibited high intra-tumoral heterogeneity (ITH) compared to treated ones, with ITH levels varying across neighboring regions in patient tumors. Differential expression analysis highlighted enriched protein and gene clusters for all patient comparisons, including innate immune proteins, macrophage activation, T- and B-cell signaling, and key cancer pathways (e.g., epithelial-mesenchymal transition, cell adhesion, notch signaling, oxidative phosphorylation and cell cycle checkpoints). Genes involved in functional processes characteristic of MBM cell types, tumor-immune interactions, and signaling mechanisms were more highly correlated with their protein levels. Overall, our results provide a comprehensive spatial and molecular view of intra-tumoral and inter-tumoral heterogeneity in MBM.
2025-07-21 | PXD055089 | Pride