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Advances in T-cell checkpoint immunotherapy for head and neck squamous cell carcinoma.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) has been found to be a complex group of malignancies characterized by their profound immunosuppression and high aggressiveness. In most cases of advanced HNSCC, treatment fails to obtain total cancer cure. Efforts are needed to develop new therapeutic approaches to improve HNSCC outcomes. In this light, T-cells "immune checkpoint" has attracted much attention in cancer immunotherapy. It has been broadly accepted that inhibitory T-cell immune checkpoints contribute to tumor immune escape through negative immune regulatory signals (cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], programmed cell death 1 [PD-1], B7-H3, and B7-H4, etc). Current data suggest that PD-1 and CTLA-4 receptors can inhibit T-cell receptors and T-cell proliferation. Blockade of PD-1/PD-L1 and/or CTLA-4/CD28 pathways has shown promising tumor outcomes in clinical trials for advanced solid tumors like melanoma, renal cell cancer, and non-small cell lung cancer. The present review attempts to explore what is known about PD-1/PD-L1 and CTLA-4/CD28 pathways with a focus on HNSCC. We further discuss how these pathways can be manipulated with therapeutic intent.

SUBMITTER: Qi X

PROVIDER: S-EPMC5716310 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Advances in T-cell checkpoint immunotherapy for head and neck squamous cell carcinoma.

Qi Xinmeng X Jia Bo B Zhao Xue X Yu Dan D

OncoTargets and therapy 20171201

Head and neck squamous cell carcinoma (HNSCC) has been found to be a complex group of malignancies characterized by their profound immunosuppression and high aggressiveness. In most cases of advanced HNSCC, treatment fails to obtain total cancer cure. Efforts are needed to develop new therapeutic approaches to improve HNSCC outcomes. In this light, T-cells "immune checkpoint" has attracted much attention in cancer immunotherapy. It has been broadly accepted that inhibitory T-cell immune checkpoi ...[more]

PMID: 29238207

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Project description:To show the relationship between antibody delivery and therapeutic efficacy in head and neck cancers, in this study we evaluated the pharmacokinetics and pharmacodynamics of epidermal growth factor receptor (EGFR)-targeted immunotherapy and radioimmunotherapy by quantitative positron emission tomography (PET) imaging.EGFR expression on UM-SCC-22B and SCC1 human head and neck squamous cell cancer (HNSCC) cells were determined by flow cytometry and immunostaining. Tumor delivery and distribution of cetuximab in tumor-bearing nude mice were evaluated with small animal PET using (64)Cu-DOTA-cetuximab. The in vitro toxicity of cetuximab to HNSCC cells was evaluated by MTT assay. The tumor-bearing mice were then treated with four doses of cetuximab at 10 mg/kg per dose, and tumor growth was evaluated by caliper measurement. FDG PET was done after the third dose of antibody administration to evaluate tumor response. Apoptosis and tumor cell proliferation after cetuximab treatment were analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Ki-67 staining. Radioimmunotherapy was done with (90)Y-DOTA-cetuximab.EGFR expression on UM-SCC-22B cells is lower than that on SCC1 cells. However, the UM-SCC-22B tumors showed much higher (64)Cu-DOTA-cetuximab accumulation than the SCC1 tumors. Cetuximab-induced apoptosis in SCC1 tumors and tumor growth was significantly inhibited, whereas an agonistic effect of cetuximab on UM-SCC-22B tumor growth was observed. After cetuximab treatment, the SCC1 tumors showed decreased FDG uptake, and the UM-SCC-22B tumors had increased FDG uptake. UM-SCC-22B tumors are more responsive to (90)Y-DOTA-cetuximab treatment than SCC1 tumors, partially due to the high tumor accumulation of the injected antibody.Cetuximab has an agonistic effect on the growth of UM-SCC-22B tumors, indicating that tumor response to cetuximab treatment is not necessarily related to EGFR expression and antibody delivery efficiency, as determined by PET imaging. Although PET imaging with antibodies as tracers has limited function in patient screening, it can provide guidance for targeted therapy using antibodies as delivery vehicles.

Dataset Information

Advances in T-cell checkpoint immunotherapy for head and neck squamous cell carcinoma.

Publications

Advances in T-cell checkpoint immunotherapy for head and neck squamous cell carcinoma.

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