A single targeted gamma-ray irradiation induced an acute modulation of immune cells and related cytokines in EMT6 mouse-bearing tumour model.

BACKGROUND A complicated interplay between radiation doses, tumour microenvironment (TME), and host immune system is linked to the active participation of immune response. OBJECTIVE The effects of single targeted 2 Gy and 8 Gy gamma-ray irradiations on the immune cell population (lymphocytes, B-cells, T-cells, neutrophils, eosinophils, and macrophages) in EMT6 mouse-bearing tumour models was investigated. METHODS The effects of both irradiation doses in early (96 hours) and acute phase (5 to 11 days) post-irradiation on immune parameters were monitored in blood circulation and TME using flow cytometry. Simultaneously, selected cytokines related to immune cells within the TME were measured using multiplex ELISA. RESULTS A temporary reduction in systemic total white blood count (TWBC) resulted from an early phase (96 hours) of gamma-ray irradiation at 2 Gy and 8 Gy compared to sham control group. No difference was obtained in the acute phase. Neutrophils dominated among other immune cells in TME in sham control group. Eosinophils in TME was significantly increased after 8 Gy treatment in acute phase compared to sham control (p< 0.005). Furthermore, the increment of tumour necrosis (TNF)-α, eotaxin and interleukin (IL)-7 (p< 0.05) in both treatment groups and phases were associated with anti-tumour activities within TME by gamma-ray irradiation. CONCLUSION The temporary changes in immune cell populations within systemic circulation and TME induced by different doses of gamma-ray irradiation correlated with suppression of several pro-tumorigenic cytokines in mouse-bearing EMT6 tumour models.

[1]  A. Goldbart,et al.  Elevated Neutrophil-to-Lymphocyte Ratio Is Associated with Severe Asthma Exacerbation in Children , 2023, Journal of clinical medicine.

[2]  Zhufeng Wang,et al.  Eosinophilia and Lung Cancer: Analysis From Real-World Data and Mendelian Randomization Study , 2022, Frontiers in Medicine.

[3]  Jie Bai,et al.  Expression of PD-L1 and CD4+ tumor-infiltrating lymphocytes predict survival in head and neck squamous cell carcinoma , 2022, Molecular and clinical oncology.

[4]  Liaoliao Dong,et al.  Neutrophils in cancer carcinogenesis and metastasis , 2021, Journal of Hematology & Oncology.

[5]  Ranvir Singh,et al.  The role of tumour-associated tissue eosinophilia as a prognostic indicator in head and neck squamous cell carcinoma , 2021, The Egyptian Journal of Otolaryngology.

[6]  V. Bours,et al.  Immunity and Breast Cancer: Focus on Eosinophils , 2021, Biomedicines.

[7]  M. Karim,et al.  Development of custom lead shield and strainer for targeted irradiation for mice in the gamma cell chamber , 2021, Scientific Reports.

[8]  S. Peters,et al.  Neutrophils in the era of immune checkpoint blockade , 2021, Journal for ImmunoTherapy of Cancer.

[9]  M. Hecht,et al.  Radiotherapy and the immune system: More than just immune suppression , 2021, Stem cells.

[10]  Kai-Ping Chang,et al.  Comparative prognostic value of different preoperative complete blood count cell ratios in patients with oral cavity cancer treated with surgery and postoperative radiotherapy , 2021, Cancer medicine.

[11]  F. Nouri,et al.  Can eosinophilia and neutrophil–lymphocyte ratio predict hospitalization in asthma exacerbation? , 2021, Allergy, Asthma & Clinical Immunology.

[12]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[13]  P. Boscolo-Rizzo,et al.  Prognostic Significance of CD4+ and CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis , 2021, Cancers.

[14]  B. Kaina,et al.  Comparison of DNA repair and radiosensitivity of different blood cell populations , 2021, Scientific Reports.

[15]  Lei Wang,et al.  Prognostic impact of eosinophils in peripheral blood and tumor site in patients with esophageal squamous cell carcinoma treated with concurrent chemoradiotherapy , 2021, Medicine.

[16]  H. Salehiniya,et al.  Delay in the diagnosis of breast cancer during coronavirus pandemic , 2021, EXCLI journal.

[17]  F. Rödel,et al.  Low dose ionizing radiation effects on the immune system , 2020, Environment international.

[18]  X. Zhang,et al.  Tumor-Associated Neutrophils and Macrophages—Heterogenous but Not Chaotic , 2020, Frontiers in Immunology.

[19]  R. Mesquita,et al.  Hypoxia and proangiogenic proteins in human ameloblastoma , 2020, Scientific Reports.

[20]  M. Malik,et al.  Assessment of toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy , 2020, Indian Journal of Cancer.

[21]  S. Caputi,et al.  COVID-19 and radiation oncology: the experience of a two-phase plan within a single institution in central Italy , 2020, Radiation oncology.

[22]  U. Jeschke,et al.  Interleukin 15 and Eotaxin correlate with the outcome of breast cancer patients vice versa independent of CTC status , 2020, Archives of Gynecology and Obstetrics.

[23]  M. Lauriola,et al.  Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies , 2020, International journal of molecular sciences.

[24]  M. Ashrafizadeh,et al.  Damage-associated molecular patterns in tumor radiotherapy. , 2020, International immunopharmacology.

[25]  Jie Wang,et al.  The presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different subsets serve as prognostic factors in advanced hypopharyngeal squamous cell carcinoma , 2020, BMC Cancer.

[26]  Esther J Pearl,et al.  The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research , 2020, PLoS biology.

[27]  A. Lancia,et al.  Radiotherapy in the era of COVID-19 , 2020, Expert review of anticancer therapy.

[28]  P. Papageorgis,et al.  The Role of Tumor-Associated Myeloid Cells in Modulating Cancer Therapy , 2020, Frontiers in Oncology.

[29]  K. Wiman,et al.  Interleukin-6 derived from cancer-associated fibroblasts attenuates the p53 response to doxorubicin in prostate cancer cells , 2020, Cell Death Discovery.

[30]  I. Jaiyesimi,et al.  Cancer treatment during COVID-19 pandemic , 2020, Medical Oncology.

[31]  S. Rey,et al.  Hypoxia: Turning vessels into vassals of cancer immunotolerance. , 2020, Cancer letters.

[32]  S. Markovic,et al.  Relevance of immune cell and tumor microenvironment imaging in the new era of immunotherapy , 2020, Journal of experimental & clinical cancer research : CR.

[33]  D. Hallahan,et al.  Radiation induces iatrogenic immunosuppression by indirectly affecting hematopoiesis in bone marrow , 2020, Oncotarget.

[34]  S. Formenti,et al.  Cancer and COVID-19 — potentially deleterious effects of delaying radiotherapy , 2020, Nature Reviews Clinical Oncology.

[35]  A. Docquier,et al.  The Emerging Role of the IL-17B/IL-17RB Pathway in Cancer , 2020, Frontiers in Immunology.

[36]  Rong Wang,et al.  CCL11 increases the proportion of CD4+CD25+Foxp3+ Treg cells and the production of IL-2 and TGF-β by CD4+ T cells via the STAT5 signaling pathway , 2020, Molecular medicine reports.

[37]  F. Marincola,et al.  Consensus guidelines for the definition, detection and interpretation of immunogenic cell death , 2020, Journal for ImmunoTherapy of Cancer.

[38]  Xikun Zhou,et al.  Tumor-Associated Macrophages: Recent Insights and Therapies , 2020, Frontiers in Oncology.

[39]  S. Gruber,et al.  The Prognostic Implications of Tumor Infiltrating Lymphocytes in Colorectal Cancer: A Systematic Review and Meta-Analysis , 2020, Scientific Reports.

[40]  Marimuthu Citartan,et al.  Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice , 2020, Frontiers in Oncology.

[41]  R. Schicho,et al.  IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils , 2020, Oncoimmunology.

[42]  M. Minopoli,et al.  Tumor Associated Neutrophils. Their Role in Tumorigenesis, Metastasis, Prognosis and Therapy , 2019, Front. Oncol..

[43]  Xiaoxia Li,et al.  The role of interleukin-17 in tumor development and progression , 2019, The Journal of experimental medicine.

[44]  Kazunari Yoshida,et al.  The role of vascular endothelial growth factor in the hypoxic and immunosuppressive tumor microenvironment: perspectives for therapeutic implications , 2019, Medical Oncology.

[45]  Stephen C. Grubb,et al.  Mouse Phenome Database: a data repository and analysis suite for curated primary mouse phenotype data , 2019, Nucleic Acids Res..

[46]  Yibing Chen,et al.  Tumor-associated macrophages: an accomplice in solid tumor progression , 2019, Journal of Biomedical Science.

[47]  C. Drake,et al.  Radiation Induces a Dose-Dependent Increase in Immunosuppressive Myeloid Cells in Solid Tumors , 2019, International Journal of Radiation Oncology, Biology, Physics.

[48]  K. D. Castle,et al.  Establishing the Impact of Vascular Damage on Tumor Response to High-Dose Radiation Therapy. , 2019, Cancer research.

[49]  J. Greenberger,et al.  Understanding the mechanism of radiation induced fibrosis and therapy options. , 2019, Pharmacology & therapeutics.

[50]  H. Cang,et al.  Crosstalk between cancer and immune cells: Role of tumor‐associated macrophages in the tumor microenvironment , 2019, Cancer medicine.

[51]  B. Poulin,et al.  Immune state is associated with natural dietary variation in wild mice Mus musculus domesticus , 2019, Functional ecology.

[52]  Wei-ping Chen,et al.  Impact of radiotherapy on immunological parameters, levels of inflammatory factors, and clinical prognosis in patients with esophageal cancer , 2019, Journal of radiation research.

[53]  Yongli Yao,et al.  Macrophage Polarization in Physiological and Pathological Pregnancy , 2019, Front. Immunol..

[54]  Lu Zhang,et al.  Immune targets in the tumor microenvironment treated by radiotherapy , 2019, Theranostics.

[55]  F. Antonicelli,et al.  The Interleukin-17 Family of Cytokines in Breast Cancer , 2018, International journal of molecular sciences.

[56]  M. Yousefi,et al.  The significant role of interleukin-6 and its signaling pathway in the immunopathogenesis and treatment of breast cancer. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[57]  A. Biete,et al.  New pre-treatment eosinophil-related ratios as prognostic biomarkers for survival outcomes in endometrial cancer , 2018, BMC Cancer.

[58]  H. de Andrade Carvalho,et al.  Radiotherapy and immune response: the systemic effects of a local treatment , 2018, Clinics.

[59]  R. V. van Lier,et al.  Functional Heterogeneity of CD4+ Tumor-Infiltrating Lymphocytes With a Resident Memory Phenotype in NSCLC , 2018, Front. Immunol..

[60]  R. Fietkau,et al.  Clinically Relevant Radiation Exposure Differentially Impacts Forms of Cell Death in Human Cells of the Innate and Adaptive Immune System , 2018, International journal of molecular sciences.

[61]  Zena Werb,et al.  Roles of the immune system in cancer: from tumor initiation to metastatic progression , 2018, Genes & development.

[62]  V. Bours,et al.  Predictive and prognostic role of peripheral blood eosinophil count in triple-negative and hormone receptor-negative/HER2-positive breast cancer patients undergoing neoadjuvant treatment , 2018, Oncotarget.

[63]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[64]  T. Eade,et al.  Radiation, inflammation and the immune response in cancer , 2018, Mammalian Genome.

[65]  I. Seto,et al.  Abscopal effect following radiation monotherapy in breast cancer: A case report. , 2018, Molecular and clinical oncology.

[66]  B. Guo,et al.  The prognostic significance of high/positive expression of tissue VEGF in ovarian cancer , 2018, Oncotarget.

[67]  T. Fujiwara,et al.  Cancer-Associated Fibroblasts Affect Intratumoral CD8+ and FoxP3+ T Cells Via IL6 in the Tumor Microenvironment , 2018, Clinical Cancer Research.

[68]  M. Shaul,et al.  Cancer‐related circulating and tumor‐associated neutrophils – subtypes, sources and function , 2018, The FEBS journal.

[69]  B. Bartosch,et al.  Synergistic effect of interleukin‐17 and tumour necrosis factor‐α on inflammatory response in hepatocytes through interleukin‐6‐dependent and independent pathways , 2018, Clinical and experimental immunology.

[70]  F. Mourtada,et al.  The Impact of Radiation on the Tumor Microenvironment: Effect of Dose and Fractionation Schedules , 2018, Cancer growth and metastasis.

[71]  Gan‐Lin Zhang,et al.  Establishment of a murine breast tumor model by subcutaneous or orthotopic implantation , 2018, Oncology letters.

[72]  A. Munitz,et al.  Mouse Eosinophils: Identification, Isolation, and Functional Analysis , 2017, Current protocols in immunology.

[73]  R. Blasberg,et al.  Impact of the Tumor Microenvironment on Tumor-Infiltrating Lymphocytes: Focus on Breast Cancer , 2017, Breast cancer : basic and clinical research.

[74]  Yifeng Gu,et al.  Radiation‐induced decrease of CD8 + dendritic cells contributes to Th1/Th2 shift , 2017, International immunopharmacology.

[75]  A. Papavassiliou,et al.  Induction of the MCP chemokine cluster cascade in the periphery by cancer cell-derived Ccl3. , 2017, Cancer letters.

[76]  A. Letai,et al.  Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages , 2017, Nature.

[77]  Minzhong Tang,et al.  Prognostic Significance of Neutrophil to Lymphocyte Ratio, Lymphocyte to Monocyte Ratio, and Platelet to Lymphocyte Ratio in Patients with Nasopharyngeal Carcinoma , 2017, BioMed research international.

[78]  Zhenggang Zhu,et al.  IL-6 secreted by cancer-associated fibroblasts promotes epithelial-mesenchymal transition and metastasis of gastric cancer via JAK2/STAT3 signaling pathway , 2017, Oncotarget.

[79]  L. Terracciano,et al.  The Interplay Between Neutrophils and CD8+ T Cells Improves Survival in Human Colorectal Cancer , 2017, Clinical Cancer Research.

[80]  V. Jendrossek,et al.  The Role of Lymphocytes in Radiotherapy-Induced Adverse Late Effects in the Lung , 2016, Front. Immunol..

[81]  S. Bobdey,et al.  Role of Monocyte Count and Neutrophil-to-Lymphocyte Ratio in Survival of Oral Cancer Patients , 2016, International Archives of Otorhinolaryngology.

[82]  P. Lambin,et al.  Fractionated Radiotherapy with 3 x 8 Gy Induces Systemic Anti-Tumour Responses and Abscopal Tumour Inhibition without Modulating the Humoral Anti-Tumour Response , 2016, PloS one.

[83]  L. Que,et al.  A Protocol for the Comprehensive Flow Cytometric Analysis of Immune Cells in Normal and Inflamed Murine Non-Lymphoid Tissues , 2016, PloS one.

[84]  A. Stevenson,et al.  Eosinophil-Associated Gene Pathways but not Eosinophil Numbers are Differentially Regulated between Synchrotron Microbeam Radiation Treatment and Synchrotron Broad-Beam Treatment by 48 Hours Postirradiation , 2015, Radiation research.

[85]  M. Disis,et al.  The Antitumor Efficacy of IL2/IL21-Cultured Polyfunctional Neu-Specific T Cells Is TNFα/IL17 Dependent , 2015, Clinical Cancer Research.

[86]  S. Lee,et al.  Radiation-induced eosinophilic, polymorphic, and pruritic eruption in a pig skin model , 2015, Laboratory animal research.

[87]  D. Tiezzi,et al.  IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment. , 2015, Cancer research.

[88]  D. Hallahan,et al.  Stem Cell Transfusion Restores Immune Function in Radiation-Induced Lymphopenic C57BL/6 Mice. , 2015, Cancer research.

[89]  F. Rödel,et al.  Radiation sensitivity of human and murine peripheral blood lymphocytes, stem and progenitor cells. , 2014, Biochimica et biophysica acta.

[90]  C. Yee,et al.  The Effect of Radiation on the Immune Response to Cancers , 2014, International journal of molecular sciences.

[91]  Paula A. Oliveira,et al.  Estimation of rat mammary tumor volume using caliper and ultrasonography measurements , 2013, Lab Animal.

[92]  Hankui Chen,et al.  Interleukin‐17 acts as double‐edged sword in anti‐tumor immunity and tumorigenesis , 2017, Cytokine.