ArticleThe Journal of clinical investigation2022
LFA-1 activation enriches tumor-specific T cells in a cold tumor model and synergizes with CTLA-4 blockade.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- How crosstalk at the immune synapse shapes T cell and dendritic cell biology.Nature reviews. Immunology · 2026Review
- Single-cell profiling of tumor lineage plasticity and the immune microenvironment in transformed small cell lung cancer.Journal of translational medicine · 2026Article
- Metal-modulated T cell antitumor immunity and emerging metalloimmunotherapy.Cancer metastasis reviews · 2025Review
- LFA-1/ICAM-1 Interactions Between CD8Cells · 2025Article
- Ribonuclease 1 Induces T-Cell Dysfunction and Impairs CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Metabolic-immune axis in the tumor microenvironment: a new strategy for prognostic assessment and precision therapy in DLBCL and FL.Frontiers in immunology · 2025Review
- Tumor cells escape immunosurveillance by hampering LFA-1.Frontiers in immunology · 2025Review
- SubvertingBiology · 2024Review
- Spatiotemporally Controlled T-Cell Combination Therapy for Solid Tumor.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mechanism of isoflurane‑mediated breast cancer growthOncology letters · 2024Article
- Immune Cell Migration to Cancer.Cells · 2024Review
- Natural Killer Cell Mechanosensing in Solid Tumors.Bioengineering (Basel, Switzerland) · 2024Review
- Motility and tumor infiltration are key aspects of invariant natural killer T cell anti-tumor function.Nature communications · 2024Article
- Conjecturing about Small-Molecule Agonists and Antagonists of α4β1 Integrin: From Mechanistic Insight to Potential Therapeutic Applications.Biomedicines · 2024Review
- ITGAL expression in non-small-cell lung cancer tissue and its association with immune infiltrates.Frontiers in immunology · 2024Article
- LFA-1 regulated by IL-2/STAT5 pathway boosts antitumor function of intratumoral CD8Oncoimmunology · 2024Article
- Lymphocyte homing and recirculation with tumor tertiary lymphoid structure formation: predictions for successful cancer immunotherapy.Frontiers in immunology · 2024Review
- Magnesium-related gene ITGAL: a key immunotherapy predictor and prognostic biomarker in pan-cancer.Frontiers in pharmacology · 2024Article
- Integrin signaling in cancer: bidirectional mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2023Review
- Abnormal generation of IL-17A represses tumor infiltration of stem-like exhausted CD8BMC medicine · 2023Article
Corrections and comments
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Authors and funding
30 authors at 5 institutions in 6 countries.
Funding
Abstract
The inability of CD8+ effector T cells (Teffs) to reach tumor cells is an important aspect of tumor resistance to cancer immunotherapy. The recruitment of these cells to the tumor microenvironment (TME) is regulated by integrins, a family of adhesion molecules that are expressed on T cells. Here, we show that 7HP349, a small-molecule activator of lymphocyte function-associated antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4) integrin cell-adhesion receptors, facilitated the preferential localization of tumor-specific T cells to the tumor and improved antitumor response. 7HP349 monotherapy had modest effects on anti-programmed death 1-resistant (anti-PD-1-resistant) tumors, whereas combinatorial treatment with anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) increased CD8+ Teff intratumoral sequestration and synergized in cooperation with neutrophils in inducing cancer regression. 7HP349 intratumoral CD8+ Teff enrichment activity depended on CXCL12. We analyzed gene expression profiles using RNA from baseline and on treatment tumor samples of 14 melanoma patients. We identified baseline CXCL12 gene expression as possibly improving the likelihood or response to anti-CTLA-4 therapies. Our results provide a proof-of-principle demonstration that LFA-1 activation could convert a T cell-exclusionary TME to a T cell-enriched TME through mechanisms involving cooperation with innate immune cells.
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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.