Plasma proteins as prognostic biomarkers in radiotherapy treated head and neck cancer patients

Brøndum, Line; Eriksen, Jesper Grau; Sørensen, Brita Singers; Mortensen, Lise Saksø; Toustrup, Kasper; Overgaard, Jens; Alsner, Jan

doi:10.1016/j.ctro.2017.01.001

Cited by 7 publications

(7 citation statements)

References 34 publications

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“…al. analyzed 19 previously described proteins in head and neck cancer patients before treatment, and they found that there was a significant difference between the baseline levels of the patient and the control group in IL-2, IL-4, EGFR, OPN, VEGFR-1, VEGFR-2, VEGF and GRO levels, but none of these markers could be correlated with outcome [31]. Widlak and his co-workers investigated changes in the proteome of head and neck cancer patients before and at various time points after irradiation and identified 55 proteins up- or downregulated post-RT compared to pre-RT values.…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy-Induced Changes in the Systemic Immune and Inflammation Parameters of Head and Neck Cancer Patients

Balázs

Kis

Badie

et al. 2019

Cancers

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Though radiotherapy is a local therapy, it has systemic effects mainly influencing immune and inflammation processes. This has important consequences in the long-term prognosis and therapy individualization. Our objective was to investigate immune and inflammation-related changes in the peripheral blood of head and neck cancer patients treated with radiotherapy. Peripheral blood cells, plasma and blood cell-derived RNA were isolated from 23 patients before and at two time points after radiotherapy and cellular immune parameters, plasma protein changes and gene expression alterations were studied. Increased regulatory T cells and increased CTLA4 and PD-1 expression on CD4 cells indicated an immune suppression induced by the malignant condition, which was accentuated by radiotherapy. Circulating dendritic cells were strongly elevated before treatment and were not affected by radiotherapy. Decreased endoglin levels in the plasma of patients before treatment were further decreased by radiotherapy. Expression of the FXDR, SESN1, GADD45, DDB2 and MDM2 radiation-response genes were altered in the peripheral blood cells of patients after radiotherapy. All changes were long-lasting, detectable one month after radiotherapy. In conclusion we demonstrated radiotherapy-induced changes in systemic immune parameters of head and neck cancer patients and proposed markers suitable for patient stratification worth investigating in larger patient cohorts.

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Section: Discussionmentioning

confidence: 99%

Radiotherapy-Induced Changes in the Systemic Immune and Inflammation Parameters of Head and Neck Cancer Patients

Balázs

Kis

Badie

et al. 2019

Cancers

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“…The patients were divided based on degree of heterogeneity as calculated by the MATH algorithm. The threshold of dichotomization of MATH high and low groups was determined by comparing differences in the overall survival between the two groups at multiple candidate cutoff points within the range of MATH, which is similar to the method previously published [24][25][26][27] .…”

Section: Survival Analysismentioning

confidence: 99%

Tumor Heterogeneity Correlates with Less Immune Response and Worse Survival in Breast Cancer Patients

et al. 2019

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Background-Intra-tumor heterogeneity implies that sub-populations of cancer cells that differ in genetic, phenotypic, or behavioral characteristics coexist in a single tumor 1,2. Tumor heterogeneity drives progression, metastasis and treatment resistance, but its relationship with tumor infiltrating immune cells is a matter of debate where some argue that tumors with high heterogeneity may generate neo-antigens that attract immune cells, and the others claim that immune cells provide selection pressure that shapes tumor heterogeneity 3,4. Here we sought to study the association between tumor heterogeneity and immune cells in a real-world cohort utilizing The Cancer Genome Atlas (TCGA). Methods-Mutant Allele Tumor Heterogeneity (MATH) was calculated to estimate intra-tumoral heterogeneity, and immune cell compositions were estimated by CIBERSORT. Survival analyses were demonstrated by Kaplan Meir curves. Results-Tumors with high heterogeneity (High MATH) associated with worse overall survival (p=0.049) as well as ER+ (p=0.011) and non-triple negative tumors (p=0.01). High MATH tumors associated with less infiltration of anti-tumor CD8 (p<0.013) and CD4 T cells (p<0.00024), more tumor promoting regulatory T cells (p<4e-04), lower expression of T cell exhaustion markers; PDL-1 (p=0.0031), IDO2 (p=0.34), ADORA2A (p=0.018), VISTA (p=0.00013), and CCR4 (p<0.00001), lower expression of cytolytic enzymes granzyme-A (p=0.0056) and perforin 1 (p=0.053) as well as low cytolytic activity score (p=0.0028). Conclusions-High heterogeneity tumors are associated with less immune cell infiltration, less activation of the immune response, and worse survival in breast cancer. Our results support the notion that tumor heterogeneity is shaped by selection pressure of tumor infiltrating immune cells.

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“…Firstly, current data on immune infiltrates and tumour cell PD-L1 expression come from pre-treatment biopsies or surgery specimens, which mainly reflect the immune status at baseline, and there is limited information on changes in TME during or post-treatment. Additionally, few data exist on systemic immune biomarkers post-RT [ 57 , 58 , 59 , 111 ]. Therefore, there is an urgent unmet clinical need to collect tumour samples and matching bloods pre- and post-RT from patients undergoing routine RT to further understand the potentially diverse impact of RT between patients and tumour types.…”

Section: Discussionmentioning

confidence: 99%

Understanding the Effects of Radiotherapy on the Tumour Immune Microenvironment to Identify Potential Prognostic and Predictive Biomarkers of Radiotherapy Response

Cheng

Cheadle

Illidge

2020

Cancers

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Radiotherapy (RT) is a highly effective anti-cancer treatment. Immunotherapy using immune checkpoint blockade (ICI) has emerged as a new and robust pillar in cancer therapy; however, the response rate to single agent ICI is low whilst toxicity remains. Radiotherapy has been shown to have local and systemic immunomodulatory effects. Therefore, combining RT and immunotherapy is a rational approach to enhance anti-tumour immune responses. However, the immunomodulatory effects of RT can be both immunostimulatory or immunosuppressive and may be different across different tumour types and patients. Therefore, there is an urgent medical need to establish biomarkers to guide clinical decision making in predicting responses or in patient selection for RT-based combination treatments. In this review, we summarize the immunological effects of RT on the tumour microenvironment and emerging biomarkers to help better understand the implications of these immunological changes, and we provide new insights into the potential for combination therapies with RT and immunotherapy.

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Plasma proteins as prognostic biomarkers in radiotherapy treated head and neck cancer patients

Cited by 7 publications

References 34 publications

Radiotherapy-Induced Changes in the Systemic Immune and Inflammation Parameters of Head and Neck Cancer Patients

Radiotherapy-Induced Changes in the Systemic Immune and Inflammation Parameters of Head and Neck Cancer Patients

Tumor Heterogeneity Correlates with Less Immune Response and Worse Survival in Breast Cancer Patients

Understanding the Effects of Radiotherapy on the Tumour Immune Microenvironment to Identify Potential Prognostic and Predictive Biomarkers of Radiotherapy Response

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