CD8 T cells are rendered exhausted in tumor and chronic infection. Among heterogeneous exhausted T cells, a subpopulation of progenitor-like (Tpex) cells have been found important for long-term tumor or pathogen control and are also the main responders in immunotherapy. Using an RFP reporter mouse for the orphan nuclear receptor NR4A1, originally characterized as critical in T cell dysfunction, we discover that the reporter is highly expressed in Tpex cells in tumor and chronic infection. Enforced expression of Nr4a1 promotes Tpex cell accumulation, whereas tumor control is improved after Nr4a1 deletion, associated with increased effector function but decreased long-term maintenance of CD8 T cells. Integrating chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis, NR4A1 is found to bind and promote the expression of Tpex-related genes, as well as suppress terminal differentiation-associated genes. This study therefore has identified a key role of NR4A1 in Tpex regulation and provides a promising target for immunotherapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.celrep.2024.114301 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Correlation between immune microenvironment and clinicopathological characteristics and prognosis of primary large B-cell lymphoma of immune-privileged sites.
Pathol Res Pract
December 2024
Department of Pathology, The Tumor Hospital Affiliated to Xinjiang Medical University, No. 789 Suzhou Dongjie, Urumqi, Xinjiang Uygur 830011, PR China. Electronic address:
Objectives: To explore the correlation between tumor-associated macrophages (TAMs), tumor-infiltrating lymphocytes (TILs), and tumor-associated angiogenesis (TAA) in the tumor microenvironment with the clinicopathological characteristics and prognosis of primary large B-cell lymphoma of immune-privileged sites (LBCL-IP).
Methods: A total of 46 cases of LBCL-IP from the Department of Pathology, the Third Affiliated Hospital of Xinjiang Medical University, from January 2010 to February 2024, were collected, along with clinical and follow-up data of LBCL-IP patients. Immunohistochemistry and triple immunofluorescence were used to detect related proteins of TAMs, TILs, and TAA, and to analyze the correlation between TAMs, TILs, TAA, and the polarization of TAMs with the clinical and prognostic factors of LBCL-IP patients.
Pre-Existing Immunity Predicts Response to First-Line Immunotherapy in Non-Small Cell Lung Cancer Patients.
Cancers (Basel)
June 2024
Laboratory of Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece.
Article Synopsis
- * A study involving 52 stage III/IV NSCLC patients showed that 44% had detectable pre-existing T cells specific to tumors, and those patients had better median overall survival rates compared to those without these T cells.
- * The research highlighted that patients with pre-existing T cells and low levels of certain immunosuppressive cells had a significant survival advantage, suggesting that evaluating these immune cell characteristics could help identify which patients are likely to benefit most from immunotherapy.
Nimodipine ameliorates liver fibrosis via reshaping liver immune microenvironment in TAA-induced in mice.
Int Immunopharmacol
September 2024
Department of Emergency Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China. Electronic address:
Nimodipine, a calcium antagonist, exert beneficial neurovascular protective effects in clinic. Recently, Calcium channel blockers (CCBs) was reported to protect against liver fibrosis in mice, while the exact effects of Nimodipine on liver injury and hepatic fibrosis remain unclear. In this study, we assessed the effect of nimodipine in Thioacetamide (TAA)-induced liver fibrosis mouse model.
View Article and Find Full Text PDFNK Receptor Signaling Lowers TCR Activation Threshold, Enhancing Selective Recognition of Cancer Cells by TAA-Specific CTLs.
Cancer Immunol Res
October 2024
Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
Cytotoxic CD8+ T lymphocyte (CTL) recognition of non-mutated tumor-associated antigens (TAA), present on cancer cells and also in healthy tissues, is an important element of cancer immunity, but the mechanism of its selectivity for cancer cells and opportunities for its enhancement remain elusive. In this study, we found that CTL expression of the NK receptors (NKR) DNAM1 and NKG2D was associated with the effector status of CD8+ tumor-infiltrating lymphocytes and long-term survival of patients with melanoma. Using MART1 and NY-ESO-1 as model TAAs, we demonstrated that DNAM1 and NKG2D regulate T-cell receptor (TCR) functional avidity and set the threshold for TCR activation of human TAA-specific CTLs.
View Article and Find Full Text PDFMolecular mimicry of SARS-COV-2 antigens as a possible natural anti-cancer preventive immunization.
Front Immunol
July 2024
Innovative Immunological Models Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Naples, Italy.
Article Synopsis
- The study explored the relationship between SARS-CoV-2 peptides and tumor-associated antigens (TAAs) to find if they could trigger similar immune responses.
- Researchers identified that many SARS-CoV-2 proteins, particularly the Spike protein from the BNT162b2 vaccine, share significant amino acid sequences with TAAs linked to various cancers like breast and melanoma.
- Findings suggest that prior infection or vaccination against COVID-19 could potentially offer immunity against certain cancers, opening avenues for developing new "multi-cancer" vaccines that exploit these viral similarities for therapeutic benefits.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!