Back to Search
Start Over
Overcoming Resistance to Combination Radiation-Immunotherapy: A Focus on Contributing Pathways Within the Tumor Microenvironment.
- Source :
-
Frontiers in immunology [Front Immunol] 2019 Jan 31; Vol. 9, pp. 3154. Date of Electronic Publication: 2019 Jan 31 (Print Publication: 2018). - Publication Year :
- 2019
-
Abstract
- Radiation therapy has been used for many years to treat tumors based on its DNA-damage-mediated ability to kill cells. More recently, RT has been shown to exert beneficial modulatory effects on immune responses, such as triggering immunogenic cell death, enhancing antigen presentation, and activating cytotoxic T cells. Consequently, combining radiation therapy with immunotherapy represents an important area of research. Thus far, immune-checkpoint inhibitors targeting programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have been the focus of many research studies and clinical trials. The available data suggest that such immunotherapies are enhanced when combined with radiation therapy. However, treatment resistance, intrinsic or acquired, is still prevalent. Various theories as to how to enhance these combination therapies to overcome treatment resistance have been proposed. In this review, we focus on the principles surrounding radiation therapy's positive and negative effects on the tumor microenvironment. We explore mechanisms underlying radiation therapy's synergistic and antagonistic effects on immune responses and provide a base of knowledge for radio-immunology combination therapies to overcome treatment resistance. We provide evidence for targeting regulatory T cells, tumor-associated macrophages, and cancer-associated fibroblasts in combination radio-immunotherapies to improve cancer treatment.
- Subjects :
- Animals
Antineoplastic Agents, Immunological pharmacology
Biomarkers, Tumor
Cancer-Associated Fibroblasts metabolism
Cancer-Associated Fibroblasts pathology
Combined Modality Therapy
Cytotoxicity, Immunologic
Endothelial Cells drug effects
Endothelial Cells radiation effects
Extracellular Matrix metabolism
Humans
Immunomodulation
Lymphocytes, Tumor-Infiltrating immunology
Lymphocytes, Tumor-Infiltrating metabolism
Lymphocytes, Tumor-Infiltrating pathology
Myeloid-Derived Suppressor Cells immunology
Myeloid-Derived Suppressor Cells metabolism
Myeloid-Derived Suppressor Cells pathology
Neoplasms etiology
Neoplasms pathology
Reactive Oxygen Species metabolism
T-Lymphocyte Subsets immunology
T-Lymphocyte Subsets metabolism
T-Lymphocyte Subsets pathology
Tumor Microenvironment drug effects
Tumor Microenvironment immunology
Tumor Microenvironment radiation effects
Antineoplastic Agents, Immunological therapeutic use
Drug Resistance, Neoplasm
Endothelial Cells metabolism
Neoplasms metabolism
Neoplasms therapy
Radiation Tolerance
Radiotherapy
Signal Transduction drug effects
Signal Transduction radiation effects
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 30766539
- Full Text :
- https://doi.org/10.3389/fimmu.2018.03154