title: Evaluation of the immune factors in the tumor environment before and after the treatment of cetuximab combined with chemotherapy.
abstract: BACKGROUND
  The effect of chemotherapy combined with monoclonal antibodies (mAbs) on the immune state of the tumor environment remains unclear and controversial. The aim of this study is to examine the effect of chemotherapy combined with cetuximab (C225, an anti-EGFR mAb) on the immune state of tumor environment, and the correlation of that effect and the clinical efficacy.
  
  
  METHODS
  Twelve patients with colorectal cancer, who received the treatment of chemotherapy combined with C225, were enrolled in this study. The tumor specimen of the primary colorectal cancer before and after treatment was obtained. The expression of a series of immune factors (TGF-β1, CD8, IL-2, TNF-α, and VEGF) was measured by immunochemistry. The expression of these immune factors before and after treatment was compared by the Wilcoxon signed-rank test. The correlation of the change of immune parameter expression after treatment and clinical efficacy was examined by chi-square tests. The correlation of the expression of immune factors, clinical efficacy, and treatment number was examined by the Spearman's correlation analysis.
  
  
  RESULTS
  There was no significant difference between the expression of TGF-β1 before and after the treatment (P >0.05). The change of TGF-β1 expression after treatment significantly correlated negatively with clinical efficacy (P = 0.05). As for CD8, IL-2, VEGF, and TNF-α, there were no significant differences between the expression before and after the treatment (P >0.05), and the change of expression after treatment also did not correlate significantly with clinical efficacy (P >0.05). The change of IL-2 expression after treatment significantly correlated negatively with treatment number (correlation coefficient = -0.585, P = 0.046). The change of TGF-β1 expression after treatment significantly correlated negatively with clinical efficacy (correlation coefficient = -0.684, P = 0.014). Before treatment, the expression of TNF-α significantly correlated positively with the expression of IL-2 (correlation coefficient = 0.629, P = 0.028). After treatment, the expression of TGF-β1 significantly correlated negatively with the expression of CD8 (correlation coefficient = -0.664, P = 0.019).
  
  
  CONCLUSIONS
  These results suggested that, in the tumor environment, the change of immune factors after treatment of cetuximab combined with chemotherapy may be associated with clinical efficacy.
authors.affiliation: Department of Medical Oncology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China. yangjunlan@csco.org.cn.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Fangfang
authors.initials: F
authors.lastname: Jing
authors.forename: Tiefeng
authors.initials: T
authors.lastname: Ji
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Guo
authors.forename: Junlan
authors.initials: J
authors.lastname: Yang
authors.forename: Shunchang
authors.initials: S
authors.lastname: Jiao
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007155:Immunologic Factors / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D059016:Tumor Microenvironment / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016827:CD8 Antigens; D007155:Immunologic Factors; D007376:Interleukin-2; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
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