ArticleOncoimmunology2016
Polyfunctional Melan-A-specific tumor-reactive CD8(+) T cells elicited by dacarbazine treatment before peptide-vaccination depends on AKT activation sustained by ICOS.
Article in Oncoimmunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 43 citations in OpenAlex.
- Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes.International journal of molecular sciences · 2024Review
- Apoptosis, a Metabolic "Head-to-Head" between Tumor and T Cells: Implications for Immunotherapy.Cells · 2024Review
- CD28/PD1 co-expression: dual impact on CD8Journal of experimental & clinical cancer research : CR · 2023Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Blood immune cells as potential biomarkers predicting relapse-free survival of stage III/IV resected melanoma patients treated with peptide-based vaccination and interferon-alpha.Frontiers in oncology · 2023Article
- T-cell repertoire diversity: friend or foe for protective antitumor response?Journal of experimental & clinical cancer research : CR · 2022Review
- Review
- Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated RetentionNano letters · 2022Article
- Polymorphic Region-Specific Antibody for Evaluation of Affinity-Associated Profile of Chimeric Antigen Receptor.Molecular therapy oncolytics · 2020Article
- Clinical and Immunological Outcomes in High-Risk Resected Melanoma Patients Receiving Peptide-Based Vaccination and Interferon Alpha, With or Without Dacarbazine Preconditioning: A Phase II Study.Frontiers in oncology · 2020Article
- Altered Peptide Ligands Impact the Diversity of Polyfunctional Phenotypes in T Cell Receptor Gene-Modified T Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Desensitized chimeric antigen receptor T cells selectively recognize target cells with enhanced antigen expression.Nature communications · 2018Article
- Single-cell multiplexed cytokine profiling of CD19 CAR-T cells reveals a diverse landscape of polyfunctional antigen-specific response.Journal for immunotherapy of cancer · 2017Article
- Tumor immunotherapy: drug-induced neoantigens (xenogenization) and immune checkpoint inhibitors.Oncotarget · 2017Review
- Advances in Immunotherapy for Melanoma: A Comprehensive Review.Mediators of inflammation · 2017Review
- Review
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The identification of activation pathways linked to antitumor T-cell polyfunctionality in long surviving patients is of great relevance in the new era of immunotherapy. We have recently reported that dacarbazine (DTIC) injected one day before peptide-vaccination plus IFN-α improves the antitumor lytic activity and enlarges the repertoire of Melan-A-specific T-cell clones, as compared with vaccination alone, impacting the overall survival of melanoma patients. To identify the mechanisms responsible for this improvement of the immune response, we have analyzed the endogenous and treatment-induced antigen (Ag)-specific response in a panel of Melan-A-specific CD8(+) T-cell clones in terms of differentiation phenotype, inhibitory receptor profile, polyfunctionality and AKT activation. Here, we show that Melan-A-specific CD8(+) T cells isolated from patients treated with chemoimmunotherapy possess a late differentiated phenotype as defined by the absence of CD28 and CD27 co-stimulatory molecules and high levels of LAG-3, TIM-3 and PD-1 inhibitory receptors. Nevertheless, they show higher proliferative potential and an improved antitumor polyfunctional effector profile in terms of co-production of TNF-α, IFNγ and Granzyme-B (GrB) compared with cells derived from patients treated with vaccination alone. Polyfunctionality is dependent on an active AKT signaling related to the engagement of the co-stimulatory molecule ICOS. We suggest that this phenotypic and functional signature is dictated by a fine-tuned balance between TCR triggering, AKT activation, co-stimulatory and inhibitory signals induced by chemoimmunotherapy and may be associated with antitumor T cells able to protect patients from tumor recurrence.
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