ArticleCancer immunology research2022
Systemic Immune Dysfunction in Cancer Patients Driven by IL6 Induction of LAG3 in Peripheral CD8+ T Cells.
Article in Cancer immunology research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Engineering "off-the-shelf" TCR-T cells: A transient mRNA platform for balanced alloreactivity and functionality.Molecular therapy. Oncology · 2026Article
- In vivo CAR-cell therapy: current challenges and emerging therapeutic advances.Molecular biomedicine · 2026Review
- Interleukin-6: The Unexpected Opponent to Pancreatic Cancer.Cellular and molecular gastroenterology and hepatology · 2026Article
- Baseline Th17/Tc17 and LAG-3 levels serve as candidate exploratory markers for early ixekizumab response in psoriasis.Frontiers in immunology · 2026Article
- The crosstalk between nerves and immunity: chronic stress as a driver of tumor progression.Frontiers in immunology · 2026Review
- Single-cell transcriptomics reveals hypoxia-driven iCAF_PLAU is associated with stemness and immunosuppression in anorectal malignant melanoma.Journal of gastroenterology · 2025Article
- Rheumatoid arthritis associated cytokines and therapeutics modulate immune checkpoint receptor expression on T cells.Frontiers in immunology · 2025Article
- Immunophenotypic analysis on circulating T cells for early diagnosis of lung cancer.Biomarker research · 2024Article
- Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.Molecular cancer · 2024Review
- T-cell and Soluble Co-inhibitory Receptor Expression in Patients With Visceral Leishmaniasis Are Markers of Treatment Response and Clinical Outcome.Open forum infectious diseases · 2024Article
- Regulatory T Cell Insufficiency in Autoimmune Diabetes Is Driven by Selective Loss of Neuropilin-1 on Intraislet Regulatory T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- LAG-3 : recent developments in combinational therapies in cancer.Cancer science · 2024Review
- Oligoclonal CD4Communications biology · 2024Article
- A combined analysis of multi-omics data reveals the prognostic values and immunotherapy response of LAG3 in human cancers.European journal of medical research · 2023Article
- Dual IL-6 and CTLA-4 blockade regresses pancreatic tumors in a T cell- and CXCR3-dependent manner.JCI insight · 2023Article
- Combinatorial blockade for cancer immunotherapy: targeting emerging immune checkpoint receptors.Frontiers in immunology · 2023Review
- High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer.iScience · 2022Article
- Molecular Pathways and Mechanisms of LAG3 in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Review
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 2 countries.
Funding
Abstract
Many cancer patients do not develop a durable response to the current standard-of-care immunotherapies, despite substantial advances in targeting immune inhibitory receptors. A potential compounding issue, which may serve as an unappreciated, dominant resistance mechanism, is an inherent systemic immune dysfunction that is often associated with advanced cancer. Minimal response to inhibitory receptor (IR) blockade therapy and increased disease burden have been associated with peripheral CD8+ T-cell dysfunction, characterized by suboptimal T-cell proliferation and chronic expression of IRs (e.g., PD1 and LAG3). Here, we demonstrated that approximately a third of cancer patients analyzed in this study have peripheral CD8+ T cells that expressed robust intracellular LAG3 (LAG3IC), but not surface LAG3 (LAG3SUR) due to a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) cleavage. This is associated with poor disease prognosis and decreased CD8+ T-cell function, which could be partially reversed by anti-LAG3. Systemic immune dysfunction was restricted to CD8+ T cells, including, in some cases, a high percentage of peripheral naïve CD8+ T cells, and was driven by the cytokine IL6 via STAT3. These data suggest that additional studies are warranted to determine if the combination of increased LAG3IC in peripheral CD8+ T cells and elevated systemic IL6 can serve as predictive biomarkers and identify which cancer patients may benefit from LAG3 blockade.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.