Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA355638 | ENA |
REPOSITORIES: ENA
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Project description:Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer
| PRJNA355634 | ENA
Project description:Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer [HNSCC]
| PRJNA355637 | ENA
Project description:Therapies that boost the anti-tumor responses of cytotoxic lymphocytes (CTLs) have shown promise in the clinic. However, clinical responses to currently available immunotherapeutic agents vary considerably, for which the molecular basis is unclear. To date, unbiased transcriptomic studies of CTLs in human cancers have been performed in whole tumors or cells obtained from peripheral blood or metastatic sites of heavily pre-treated patients. We performed global transcriptional profiling of CTLs in tumors and adjacent non-tumor tissue from treatment-naïve patients with early stage lung cancer to define the molecular features associated with robustness of anti-tumor immune responses. We observed major differences in the transcriptional program of tumor-infiltrating CTLs that are shared across tumor subtypes. Pathway analysis revealed enrichment of genes in cell cycle, T cell receptor (TCR) activation and co-stimulation pathways, indicating tumor-driven expansion of presumed tumor antigen-specific CTLs. We also observed marked heterogeneity in the expression of molecules associated with TCR activation and immune checkpoints such as 4-1BB, PD1, TIM3, and their expression was positively correlated with the density of tumor-infiltrating CTLs. Interestingly, transcripts linked to tissue-resident memory cells (TRM), such as CD103, were enriched in tumors containing a high density of CTLs, and CTLs from CD103high tumors displayed features of enhanced cytotoxicity, implying better anti-tumor activity. In an independent cohort of 689 lung cancer patients, we confirmed that patients with CD103high (TRM rich) tumors survived significantly longer. In summary, we define the molecular fingerprint of tumor-infiltrating CTLs at the site of primary tumor and identify a number of novel targets that may be important in modulating the magnitude and specificity of anti-tumor immune responses in lung cancer.
2017-06-19 | GSE90729 | GEO
Project description:Therapies that boost the anti-tumor responses of cytotoxic lymphocytes (CTLs) have shown promise in the clinic. However, clinical responses to currently available immunotherapeutic agents vary considerably, for which the molecular basis is unclear. To date, unbiased transcriptomic studies of CTLs in human cancers have been performed in whole tumors or cells obtained from peripheral blood or metastatic sites of heavily pre-treated patients. We performed global transcriptional profiling of CTLs in tumors and adjacent non-tumor tissue from treatment-naïve patients with early stage lung cancer to define the molecular features associated with robustness of anti-tumor immune responses. We observed major differences in the transcriptional program of tumor-infiltrating CTLs that are shared across tumor subtypes. Pathway analysis revealed enrichment of genes in cell cycle, T cell receptor (TCR) activation and co-stimulation pathways, indicating tumor-driven expansion of presumed tumor antigen-specific CTLs. We also observed marked heterogeneity in the expression of molecules associated with TCR activation and immune checkpoints such as 4-1BB, PD1, TIM3, and their expression was positively correlated with the density of tumor-infiltrating CTLs. Interestingly, transcripts linked to tissue-resident memory cells (TRM), such as CD103, were enriched in tumors containing a high density of CTLs, and CTLs from CD103high tumors displayed features of enhanced cytotoxicity, implying better anti-tumor activity. In an independent cohort of 689 lung cancer patients, we confirmed that patients with CD103high (TRM rich) tumors survived significantly longer. In summary, we define the molecular fingerprint of tumor-infiltrating CTLs at the site of primary tumor and identify a number of novel targets that may be important in modulating the magnitude and specificity of anti-tumor immune responses in lung cancer.
2017-06-19 | GSE90728 | GEO
Project description:How tissue resident memory CD4 T cell differ from circulating memory CD4 T cells and how such differences impact functional recall responses to pathogens is unknown. We used microarrays to detail the global programme of gene expression underlying differences between sort purified circulating memory CD4 T cells from the lung and spleen, which are labelled with flourescent antibody following intravenous administration, and lung tissue resident memory CD4 T cells, which are not labelled with flourescent antibody following intravenous administration, on day 28 post influenza infection.
2020-10-18 | GSE105257 | GEO
Project description:Current cancer immunotherapies promote recovery of CD103+ tissue-resident memory T cells (Trm) population of the tumor-infiltrating T lymphocytes (TILs). However, not all treated patients exhibit improved anti-tumor immunity and survival, likely due to the immunophenotypical diversity among the CD103+ Trm TILs. Utilising multifaceted proteomics approaches and patients’ clinical analyses, we discovered an unusual subset of CD8+ Trm TILs expressing non-canonical integrin β3 early during T cells activation. The integrin β3 surprisingly heterodimerises with CD103 on T cells, leading to unconventional granulysin-mediated cytotoxicity, elevated alternative bioenergy usage and efficient T cell migration, with minimal overall exhaustion. Importantly, early-stage non-small cell lung carcinoma (NSCLC) patients with enriched presence of integrin β3+CD103+ Trm TILs exhibited better clinical prognosis, with improved T cell immunophenotype, hence confirming the beneficial role of this unusual subset of Trm TILs. These unconventional anti-tumor T cell features provide new avenues and future opportunities for designing better translational immunotherapy strategies.
2024-02-14 | PXD031794 | Pride
Project description:Tissue-resident memory T (TRM) cells are crucial mediators of adaptive immunity in non-lymphoid tissues. However, the functional heterogeneity and pathogenic roles of CD4+ TRM cells that reside within chronic inflammatory lesions remain unknown. We found that CD69hiCD103low CD4+ TRM cells produced effector cytokines and promoted the inflammation and fibrotic responses induced by chronic exposure to Aspergillus fumigatus. Simultaneously, immunosuppressive CD69hiCD103hiFoxp3+ CD4+ regulatory T (Treg) cells were induced and constrained the ability of pathogenic CD103low TRM cells to cause fibrosis. Thus, lung tissue-resident CD4+ T cells play crucial roles in the pathology of chronic lung inflammation, and CD103 expression defines pathogenic effector and immunosuppressive tissue-resident cell subpopulations in the inflamed lung.
2020-06-30 | GSE133399 | GEO
Project description:Tissue health is dictated by the capacity to respond to perturbations and then return to homeostasis. Mechanisms that initiate, maintain, and regulate immune responses in tissues are therefore essential. Adaptive immunity plays a key role in these responses, with memory and tissue-residency being cardinal features. A corresponding role for innate cells is unknown. Here we have identified a population of innate lymphocytes that we term tissue-resident memory-like natural killer (NKRM) cells. In response to murine cytomegalovirus infection, we show that circulating NK cells were recruited in a CX3CR1-dependent manner to the salivary glands where they formed NKRM cells, a long-lived tissue-resident population that prevented autoimmunity via TRAIL-dependent elimination of CD4+ T cells. Thus, NK cells develop adaptive-like features, including long-term residency in nonlymphoid tissues, to modulate inflammation, restore immune equilibrium and preserve tissue health. Modulating the functions of NKRM cells may provide additional strategies to treat inflammatory and autoimmune diseases.
2023-02-13 | GSE222613 | GEO
Project description:Tissue health is dictated by the capacity to respond to perturbations and then return to a homeostatic state. Thus, mechanisms that initiate, maintain and regulate immune responses in tissues are essential. The adaptive immune system has been ascribed a principal role in these responses, with memory and tissue-residency being cardinal features of immune protection in tissues. Whether there is a corresponding role for innate cells is unknown. Here we identify a population of innate lymphocytes that we term tissue-resident memory-like natural killer (NKRM) cells. In response to murine cytomegalovirus infection, we show that circulating NK cells are recruited to the salivary glands where they form NKRM cells, a long-lived tissue-resident population that prevents autoimmunity and safeguards organ function. Thus, NK cells develop adaptive-like features, including long-term residency in nonlymphoid tissues, to modulate inflammation, restore immune equilibrium and preserve tissue health. Modulating the functions of NKRM cells may provide new strategies to treat inflammatory and autoimmune diseases.
2023-02-13 | GSE219243 | GEO
Project description:Purpose: To create a radiogenomic map linking computed tomographic (CT) image features and gene expression profiles generated by RNA sequencing for patients with non-small cell lung cancer (NSCLC). Methods: A cohort of 113 patients with NSCLC diagnosed between April 2008 and September 2014 who had preoperative CT data and tumor tissue available was studied. For each tumor, a thoracic radiologist recorded 87 semantic image features, selected to reflect radiologic characteristics of nodule shape, margin, texture, tumor environment, and overall lung characteristics. Next, total RNA was extracted from the tissue and analyzed with RNA sequencing technology. Ten highly coexpressed gene clusters, termed metagenes, were identified, validated in publicly available gene-expression cohorts, and correlated with prognosis. Next, a radiogenomics map was built that linked semantic image features to metagenes by using the t statistic and the Spearman correlation metric with multiple testing correction. Results: RNA sequencing analysis resulted in 10 metagenes that capture a variety of molecular pathways, including the epidermal growth factor (EGF) pathway. A radiogenomic map was created with 32 statistically significant correlations between semantic image features and metagenes. Conclusions: Radiogenomic analysis of NSCLC showed multiple associations between semantic image features and metagenes that represented canonical molecular pathways
2018-08-03 | GSE103584 | GEO