Aberrant Expressions of Immune Factors Facilitate the Disequilibrium of Immune Status in Cervical Cancer.
Objective To explore the expressions and co-relationship of immune factors forkhead box p3 (FoxP3),chemokine (C-C motif) ligand 22 (CCL22),tumor necrosis factor receptor superfamily member 40(OX40),and SMAD family member 3 (Smad3) in cervical carcinoma and investigate their immunomodulatory roles in cervical carcinogenesis.Methods Totally 30 cases of cervical carcinoma with adjacent tissues and 20 cases of normal cervix were collected in this study. FoxP3,CCL22,OX40,and Smad3 mRNA expressions were detected by real-time polymerase chain reaction (RT-PCR). Results Compared to normal cervix,the expression levels of FoxP3 and CCL22 mRNA were elevated in neoplastic foci(P=0.000,P=0.002) and tumor periphery (P=0.048,P=0.040).The mRNAs increased modestly in high-grade squamous cell carcinoma focal(P=0.019,P=0.020) and periphery tissue (P=0.023,P=0.031) in comparison with low-grade squamous cell carcinoma. The expression levels of OX40 and Smad3 mRNA were significantly lower in neoplastic foci(P=0.000,P=0.015) than normal cervix. Compared to low-grade squamous cell carcinoma focal and periphery tissue,the mRNAs decreased moderately in high-grade squamous cell carcinoma(P=0.018,P=0.030; P=0.027,P=0.014). In both neoplastic foci and tumor periphery,the mRNA expression level of CCL22 was positively correlated with FoxP3 (r=0.353,P=0.000; r=0.307,P=0.000) but negatively correlated with OX40 (r=-0.288,P=0.031; r=-0.263,P=0.037),while OX40 was positively correlated with Smad3 (r=0.384,P=0.002;r=0.288,P=0.023). The mRNA expressions of FoxP3 and CCL22 were increased in foci and pericarcinous tissues (P=0.024,P=0.039; P=0.032,P=0.034) while Smad3 was decreased in neoplastic foci (P=0.017) in contrast to HPV negative corresponding group. Conclusion FoxP3 and CCL22 expressions increase while OX40 and Smad3 expression decrease at mRNA level in the microenvironment of cervical cancer,which may be associated with such immunological model that the immunosuppressive roles of FoxP3 and CCL22 enhance while the immunity-boosting roles of OX40 and Smad3 are impeded,contributing to the deterioration of immune disequilibrium in local site and cervical cancer carcinogenesis.
Department of Obstetrics and Gynecology,the First Affiliated Hospital, Xi'an Jiaotong University,Xi'an 710061,China.
Min-Yi
MY
Zhao
Department of Obstetrics and Gynecology,the First Affiliated Hospital, Xi'an Jiaotong University,Xi'an 710061,China.
Juan
J
Zhao
Department of Obstetrics and Gynecology,the First Affiliated Hospital, Xi'an Jiaotong University,Xi'an 710061,China.
Ting
T
Yang
Department of Obstetrics and Gynecology,the First Affiliated Hospital, Xi'an Jiaotong University,Xi'an 710061,China.
Li
L
Wang
Department of Obstetrics and Gynecology,the First Affiliated Hospital, Xi'an Jiaotong University,Xi'an 710061,China.
Mei-Li
ML
Pei
Department of Obstetrics and Gynecology,the First Affiliated Hospital, Xi'an Jiaotong University,Xi'an 710061,China.
Si-Juan
SJ
Tian
Department of Obstetrics and Gynecology,the First Affiliated Hospital, Xi'an Jiaotong University,Xi'an 710061,China.
Yang
Y
Yu
Department of Obstetrics and Gynecology,the First Affiliated Hospital, Xi'an Jiaotong University,Xi'an 710061,China.
Xiao-Feng
XF
Yang
D002294:Carcinoma, Squamous Cell / Q000276:immunology; D054422:Chemokine CCL22 / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D053262:Receptors, OX40 / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000276:immunology*
C515482:CCL22 protein, human; D054422:Chemokine CCL22; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D053262:Receptors, OX40; C497790:SMAD3 protein, human; D051900:Smad3 Protein; C505716:TNFRSF4 protein, human