title: In situ observation of the effects of local irradiation on cytotoxic and regulatory T lymphocytes in cervical cancer tissue.
abstract: Local radiotherapy is the major therapeutic approach to control inoperable cervical cancer. In this study, we analyzed the local immune microenvironment of cervical cancer before and after clinical radiation therapy to investigate whether tumor response due to immunomodulation. A total of 59 patients with pathologically diagnosed cervical cancers classified according to the International Federation of Obstetrics and Gynecology (FIGO) criteria were recruited. The patients were treated according to their disease status with standard radiation regimens. For each patient, tumor biopsies were conducted before, during and after radiation treatment with the doses of 0, 10, 20 and 30 Gy, respectively. All of the tumor samples were then grouped according to the doses delivered and tumor infiltrating lymphocytes with the biomarkers of CD8, CD4, FOXP3 and OX40 were measured by in situ immunohistochemistry. We found that before radiation treatment both CD8(+) T cell and CD4(+) T cell infiltrates were more present in the tumor stroma than in the tumor nests, while OX40(+) and FOXP3(+) T cell infiltrates were present at similar levels in both the tumor nests and stroma. After radiation treatment, the levels of CD8(+) T cells and CD4(+) T cells in the tumor nests and stroma were decreased compared with the levels before irradiation. However, OX40(+) T cells and FOXP3(+) T cells did not show any difference before and after irradiation, which indicates that the FOXP3(+) T cells were more resistant to ionizing radiation than were the cytotoxic effector T cells and demonstrates a dynamic rebalance of infiltrating lymphocytes in the tumor milieu occurs after radiotherapy. This suggest that local antitumor immunity could be compromised due to decreased cytotoxic effector cells and the relatively stable status of FOXP3(+) T cells after irradiation. Therefore, regulation of these FOXP3(+) T cells may be a potentially effective approach to enhance the efficacy of cancer radiation therapy.
authors.affiliation: Institute of Molecular Radiobiology of Cancer, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P R China.
authors.forename: Shi
authors.initials: S
authors.lastname: Qinfeng
authors.forename: Wang
authors.initials: W
authors.lastname: Depu
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiaofeng
authors.forename: Walayat
authors.initials: W
authors.lastname: Shah
authors.forename: Chen
authors.initials: C
authors.lastname: Hongwei
authors.forename: Wang
authors.initials: W
authors.lastname: Yili
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D053262:Receptors, OX40 / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D059016:Tumor Microenvironment / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human