Dendritic Cells, the T-cell-inflamed Tumor Microenvironment, and Immunotherapy Treatment Response
| Autor: | Christopher Garris, Jason J. Luke |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Chemokine T-Lymphocytes T cell medicine.medical_treatment Cell Communication Biology Article 03 medical and health sciences Lymphocytes Tumor-Infiltrating 0302 clinical medicine Immune system Cancer immunotherapy Neoplasms Antineoplastic Combined Chemotherapy Protocols Tumor Microenvironment medicine Animals Humans Immune Checkpoint Inhibitors Wnt Signaling Pathway Tumor microenvironment Innate immune system Cancer Dendritic Cells Immunotherapy medicine.disease Disease Models Animal 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research biology.protein |
| Zdroj: | Clin Cancer Res |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-19-1321 |
| Popis: | The development of the most successful cancer immunotherapies in solid tumors, immune-checkpoint blockade, has focused on factors regulating T-cell activation. Until recently, the field has maintained a predominately T-cell centric view of immunotherapy, leaving aside the impact of innate immunity and especially myeloid cells. Dendritic cells (DC) are dominant partners of T cells, necessary for initiation of adaptive immune responses. Emerging evidence supports a broader role for DCs in tumors including the maintenance and support of effector functions during T-cell responses. This relationship is evidenced by the association of activated DCs with immune-checkpoint blockade responses and transcriptional analysis of responding tumors demonstrating the presence of type I IFN transcripts and DC relevant chemokines. T-cell-inflamed tumors preferentially respond to immunotherapies compared with non–T-cell-inflamed tumors and this model suggests a potentially modifiable spectrum of tumor microenvironmental immunity. Although host and commensal factors may limit the T-cell-inflamed phenotype, tumor cell intrinsic factors are gaining prominence as therapeutic targets. For example, tumor WNT/β-catenin signaling inhibits production of chemokine gradients and blocking DC recruitment to tumors. Conversely, mechanisms of innate immune nucleic acid sensing, normally operative during pathogen response, may enhance DC accumulation and make tumors more susceptible to cancer immunotherapy. Elucidating mechanisms whereby DCs infiltrate and become activated within tumors may provide new opportunities for therapeutic intervention. Conceptually, this would facilitate conversion of non–T-cell-inflamed to T-cell-inflamed states or overcome secondary resistance mechanisms in T-cell-inflamed tumors, expanding the proportion of patients who benefit from cancer immunotherapy. |
| Databáze: | OpenAIRE |
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