ArticleOncoimmunology2020
LAG-3 and PD-1+LAG-3 inhibition promote anti-tumor immune responses in human autologous melanoma/T cell co-cultures.
Article in Oncoimmunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
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- Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer.Experimental hematology & oncology · 2025Review
- Immune-based cancer therapies: mechanistic insights, clinical progress, and future directions.Journal of the Egyptian National Cancer Institute · 2025Review
- Unraveling Relatlimab-Specific Biology Using Biomarker Analyses in Patients with Advanced Melanoma in RELATIVITY-047.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- SITC vision: Opportunities for deeper understanding of mechanisms of anti-tumor activity, toxicity, and resistance to optimize cancer immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.Journal of hematology & oncology · 2025Review
- Tumor-infiltrating lymphocytes and tumor-associated macrophages in cancer immunoediting: a targetable therapeutic axis.Frontiers in immunology · 2025Review
- The role of immune checkpoint molecules in cancers.Frontiers in immunology · 2025Review
- LAG-3-An incompletely understood target in cancer therapy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Review
- Deciphering LAG-3: unveiling molecular mechanisms and clinical advancements.Biomarker research · 2024Review
- Resveratrol suppresses liver cancer progression by downregulating AKR1C3: targeting HCC with HSA nanomaterial as a carrier to enhance therapeutic efficacy.Apoptosis : an international journal on programmed cell death · 2024Article
- The Immune Checkpoint BTLA in Oral Cancer: Expression Analysis and Its Correlation to Other Immune Modulators.International journal of molecular sciences · 2024Article
- Progress of lymphocyte activation gene 3 and programmed cell death protein 1 antibodies for cancer treatment: A review.Biomolecules & biomedicine · 2024Review
- Review
- BTLA biology in cancer: from bench discoveries to clinical potentials.Biomarker research · 2024Review
- Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors.Frontiers in immunology · 2024Review
- Advances in immunotherapy for mucosal melanoma: harnessing immune checkpoint inhibitors for improved treatment outcomes.Frontiers in immunology · 2024Review
- LAG3 immune inhibitors: a novel strategy for melanoma treatment.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the success of immunotherapy using checkpoint blockade, many patients with solid tumors remain refractory to these treatments. In human cancer, the experimental options to investigate the specific effects of antibodies blocking inhibitory receptors are limited and it is still unclear which cell types are involved. We addressed the question whether the direct interaction between T cells and tumor cells can be enforced through blocking a set of inhibitory receptors including PD-1, TIM-3, BTLA and LAG-3, blocked either individually or in dual combinations with the anti-PD-1 antibody, and to determine the condition that induces maximal T cell function preventing tumor cell proliferation. Using short-term Melan-A-specific or autologous re-stimulations, checkpoint blockade did not consistently increase cytokine production by tumor-derived expanded T cells. We next set up a 5-day co-culture assay with autologous melanoma cell lines and expanded tumor infiltrating T cells, originating from tumor specimens obtained from 6 different patients. Amongst all combos tested, we observed that blockade of LAG-3 alone, and more strongly when combined with PD-1 blockade, enforced T cell responses and tumor cell growth control. The combination of anti-LAG-3 plus anti-PD-1 acted through CD8 T cells and led to increased IFNγ production and cytotoxic capacity. Our results show that LAG-3 and PD-1 are regulating the direct interaction between tumor cells and autologous T cells, suggesting that therapy effects may be promoted by enhanced access of the corresponding blocking reagents to the tumor microenvironment.
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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.