| Objective: 1)To analyze the relationship between T cell subsets and clinical pathological characteristics and prognosis of patients with cervical squamous cell carcinoma in Tumour Hospital affiliated to Xinjiang Medical University from January2015 to June 2019.2)To analyze the correlation between KLRG1 and 2B4 expression and clinical pathological features in patients with advanced cervical cancer.3)To analyze he levels of IFN-?,IL-13,IL-2,MIP-1? and TNF-? of SALL4-specific CD4+T and CD8 + T cells in patients with advanced cervical cancer.Methods:1)A total of 393 patients with stage IIB?IVA cervical squamous cell carcinoma confirmed by histopathology in Tumor Hospital affiliated to Xinjiang Medical University were collected,and the relationship between the clinical pathology characteristics of T cell subsets and prognosis was analyzed.2)Peripheral blood and cervical tissue specimens were collected from patients with stage IIB?IVA of cervical cancer squamous cell carcinoma treated for the first time in the Tumor Hospital affiliated to Xinjiang Medical University.Flow cytometry was used to detect the expression of 2B4 and KLRG1 in CD4 + T cells and CD8 + T cells in cancer tissues and peripheral blood of patients before primary treatment and end of treatment.The differences in the levels of 2B4 and KLRG1 expressed by CD4 + T cells and CD8 + T cells in peripheral venous blood and cancer tissues were analyzed and their clinical significance in tumorigenesis and development.To further explore the changes in the expression levels of KLRG1 and 2B4 in peripheral blood of patients before and after radiotherapy and its impact on clinical efficacy,to provide a theoretical basis for patients with advanced cervical cancer with radiotherapy combined with immunotherapy,and to promote individualized treatment of cervical cancer.3)The expression of IFN-?,IL-13,IL-2,MIP-1? and TNF-? was detected by intracellular cytokine staining in PBMCs of patients with IIB?IVA cervical squamous cell carcinoma and healthy controls stimulated by SALL4 antigen peptide.Results:1)There were 393 cases of cervical squamous cell carcinoma of IIB?IVA stage.T cell subgroup analysis results showed that CD8 + T cells,CD4 + T / CD8 + T are related to clinical stage of cervical cancer and tumor diameter(P<0.05).The later the tumor FIGO stage,the larger the tumor diameter,the higher the CD8+ T cells and the lower of CD4 + T / CD8 + T ratio.The higher the level of SCC-Ag,the higher the CD8+T cells in the peripheral blood of cervical squamous cell carcinoma.SCC-Ag levels are related to FIGO stage,tumor diameter,lymph node metastasis and HPV infection.The later the tumor FIGO stage,the larger the tumor diameter,the lymph node metastasis and patients with HPV infection,the higher the level of SCC-Ag in patients.Log-rank univariate analysis showed that FIGO stage and tumor diameter had significant effects on the PFS of patients(P <0.001).The tumor FIGO stage(P <0.001)and tumor diameter(P=0.004)and treatment(P <0.001)had significant effects on the patient's OS.COX multivariate analysis showed that BMI value,tumor FIGO stage,treatment method and HPV infection are independent factors that affect patients' PFS.BMI value,tumor FIGO stage,treatment method and SCC-Ag levels are independent factors that affect patients' OS.CD4 + T,CD8 + T cells,CD4+ T/CD8+ T have nothing to do with PFS and OS.2)Compared with healthy controls,the expression level of KLRG1 on CD8+T cells in peripheral venous blood specimens of patients with cervical cancer was significantly increased(P = 0.0056).The expression of 2B4 on CD8 + T cells in peripheral venous blood of patients with cervical cancer was significantly higher than that of healthy controls(P = 0.0441).KLRG1 expressed on CD8+T cells in peripheral venous blood was significantly higher than that in tumor tissues(P <0.0001).2B4 expressed on CD4+T cells in peripheral venous blood was significantly higher than that in tumor tissues(P=0.0003).The relationship between KLRG1 expression on CD4 + T and CD8 + T cells and clinical features showed that KLRG1 expression in CD8 + T cells is related to age and HPV infection.68 patients with cervical cancer had a median age of 54 years.The expression level of KLRG1 on CD8 + T cells in patients who were older than 54 years old in peripheral venous blood was significantly higher than that of patients younger than 54years(P= 0.001).The expression level of CD8 + T cells on peripheral venous blood in 12HPV-negative cervical cancer patients was higher than 56 HPV-positive cervical cancer patients(P = 0.026).The expression of 2B4 in CD8 + T cells is related to age and menopause.The expression of 2B4 in peripheral venous blood CD8 + T cells of patients with cervical cancer aged ?54 years is significantly higher than that of patients <54 years old(P <0.001).The expression of KLRG1 on CD8 + T cells of menopausal cervical cancer patients was significantly higher than that of cervical cancer patients without menopause(P = 0.006).The expression level of KLRG1 on CD8 + T cells in cervical cancer tissues patients with pelvic lymph node metastasis was significantly higher than that of patients with on pelvic lymph node metastasis(P=0.016).Thirty-four patients with cervical cancer collected peripheral venous blood at the end of treatment.Analysis showed that KLRG1 expression on CD4 + T(P = 0.0158)and CD8 + T(P = 0.0187)cells was higher than that before radiotherapy.The patients who had higher expression level of KLRG1 on CD4 + T cells in cervical cancer tissues had a lower objective response rate.3)The level of IL-2,IL-13,IFN-? and TNF-? on CD4+T cells in patients with advanced cervical squamous cell carcinoma was higher than that of healthy controls,and the difference was statistically significant(P<0.05),while the level of MIP-1? had no significant difference(P=0.827).The level of IL-2 on CD8+T cells in patients with advanced cervical squamous cell carcinoma was higher than that of healthy controls(P=0.019),while the level of IL-13?IFN-??TNF-? and MIP-1? had no significant difference(P>0.05).Conclusion: 1)CD8+T cells and CD4+T/CD8+T are related to clinical stage and tumor diameter of cervical cancer.The later the tumor FIGO stage,the larger the tumor diameter,the higher the CD8 + T cells and the lower the CD4 + T/CD8 + T ratio.Cervical cancer patients 'BMI value,tumor FIGO stage,and treatment methods are important factors that affect patients' PFS and OS.CD4 + T cells,CD8 + T cells,CD4+ T/CD8+T had no significant effect on PFS and OS of patients.2)KLRG1 and 2B4 can be detected in CD4 + T and CD8 + T cells in peripheral venous blood and cancer tissues of patients with advanced cervical squamous cell carcinoma.The expression of KLRG1 on the surface of CD8 + T cells in peripheral venous blood is closely related to age and HPV infection.The expression of KLRG1 on CD8+ T cells in cervical cancer tissues is closely related to pelvic lymph nodes.The expression of 2B4 on the surface of CD8+ T cells in peripheral venous blood is closely related to age and history of menopause.Radiotherapy can cause changes in the immune system of patients with cervical squamous cell carcinoma.The expression level of KLRG1 on CD4+T and CD8+T cells after radiotherapy is significantly lower than before radiotherapy.To provide guidance for the use of cervical cancer radiotherapy combined with immunotherapy.3)SALL4 antigen peptide is used to stimulate PBMCs in patients with advanced cervical squamous cell carcinoma.SALL4 antigen peptide may become an effective cell stimulator for cervical cancer.IL-2,IL-13,IFN-?,and TNF-? in CD4+T cells in patients with advanced cervical squamous cell carcinoma were higher than those in healthy controlsand IL-2 in CD8+T cells in patients with advanced cervical squamous cell carcinoma were higher than those in healthy controls.Using intracellular cytokine staining technique can more accurately determine the proportion and function of CD4+T cells and CD8+T cell subsets secreting multiple cytokines in patients with advanced cervical squamous cell carcinoma. |
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