| [Objective]Part ?:Myeloid-derived suppressor cells(MDSCs)represent a heterogeneous population of myeloid progenitor cells with immune suppressive function and has emerged as one of the central regulators of immune responses in cancer.In our previous studies,we found that in Fc?RIIb-/-tumor-bearing mice,splenic MDSCs exhibited a lower IL-10,PGE2 and TGF-?expression but a higher TNF-? and IFN-? expression.Fc?IIRb-/-MDSCs significantly retard the growth of subcutaneous tumors.We hypothesized that Fc?RIIb deficiency may manipulate MDSCs polarization from immunosuppressive to immunostimulating phenotype.In this study,we will further determine the expression of Fc?RIIb on peripheral blood MDSCs and its clinical significance.Partll:B cells positively regulate immune responses through antibody production and antigen presenting.Also,regulatory B cells have been recently identified and play important roles in the immune hematostasis.In our previous studies,a distinct regulatory B subset,CD19h,Fc?IIbbi Bregs,which preferentially secret IL-10 and have regulatory functions in vitro and in vivo.In this study,we will detect the proportion of CD19+Fc?RIIbbi B cells to CD19+B cells in the peripheral blood of patients with skin cancer and lung cancer and its clinical significance.[Methods]Part ?:From March 2017 to December 2018,a total of 20 patients with Cutaneum Carcinoma diagnosed in dermatology,burn orthopaedics and pathology departments of north Jiangsu people's hospital were collected,including 10 males and 10 females.There were 6 cases of cutaneous squamous cell carcinoma,8 cases of basal cell carcinoma,3 cases of Bowen's disease and 3 cases of malignant melanoma.There were 4 cases with metastatic cutaneous malignancy and 16 cases without metastatic cutaneous malignancy.A tatal of 89 peripheral blood samples were collected from patients diagnosed with lung cancer in the department of respiratory medicine and the department of oncology of north Jiangsu people's hospital,including 71 males and 18 females with lung cancer,with a ratio of 4:1,age:43-81 years old,median age:62 years old.According to different pathological types,27 cases of lung small cell carcinoma,28 cases of lung squamous cell carcinoma,and 34 cases of lung adenocarcinoma;TNM stage ?/?a stage in 12 cases,?b/?/? stage in 77 cases;the infiltration degree was Tl-2 in 20 cases and T3-4 in 69 cases.There were 16 cases with lymph node metastasis and 73 cases without lymph node metastasis.Peripheral blood samples were collected from 33 normal subjects,including 18 males and 15 females,with a male to female ratio of 6:5.The median age was 33 years old.All peripheral blood samples were taken from the blood routine examination on the same day,and the consent of the patient was obtained.In this study,the average expression of Fc?RIIb on MDSCs in peripheral blood of normal people,patients with skin malignancies and lung cancer were detected by flow cytometry.Combined with the clinicopathologic data of the patients,its clinical significance was analyzed with Prism6.0 software.Part ?:From March 2017 to December 2018,a total of 20 patients with Cutaneum Carcinoma diagnosed in dermatology,bun orthopaedics and pathology departments of north Jiangsu people's hospital were collected,including 10 males and 10 females.There were 6 cases of cutaneous squamous cell carcinoma,8 cases of basal cell carcinoma,3 cases of Bowen's disease and 3 cases of malignant melanoma.There were 4 cases with metastatic cutaneous malignancy and 16 cases without metastatic cutaneous malignancy.A tatal of 87 peripheral blood samples were collected from patients diagnosed with lung cancer in the department of respiratory medicine and the department of oncology of north Jiangsu peopled hospital,including 69 males and 18 females with lung cancer,with a ratio of 23:6,age:45-80 years old,median age:62.5 years old.According to different pathological types,22 cases of lung small cell carcinoma,31 cases of lung squamous cell carcinoma,and 34 cases of lung adenocarcinoma;TNM stage ?/?a stage in 15 cases,?b/?/? stage in 72 cases;the infiltration degree was Tl-2 in 36 cases and T3-4 in 51 cases.There were 25 cases with lymph node metastasis and 62 cases without lymph node metastasis.Peripheral blood samples were collected from 30 normal subjects,including 16 males and 14 females,with a male to female ratio of 8:7.The median age was 30 years old.All peripheral blood samples were taken from the blood routine examination on the same day,and the consent of the patient was obtained.In this study,flow assay was used to detect the frequency of CD19rhlFc?RIIbhi B cell in peripheral blood.Combined with the clinicopathologic data of the patients,its clinical significance was analyzed with Prism6.0.[Results]Part I:The average expression of Fc?RIIb in peripheral blood MDSCs of patients with Cutaneum Carcinoma were not significantly different from that of normal controls(P=0.201).The average expression of Fc?RIIb on MDSCs in patients with lung malignant tumor were obviously up-regulated compared with that of normal controls(P=0.002)and the lung adenocarcinoma raised the most obvious(P=0.004).The average expression of Fc?RIIb on MDSCs in patients with lung cancer was associated with TNM stage(P=0.006)and metastasis(P=0.023),but not with the degree of tumor infiltration(P=0.757)s gender(P=0.326)and age(P=0.427).Part ?:The frequency of CD19+Fc?RIIbhiB cells in peripheral blood CD19+B cells of patients with Cutaneum Carcinoma showed no significant difference from that of normal controls(P=0.685).The frequency of CD 19+Fc?RIIbhiB cells in pulmonary malignant tumor patients is higher than that of normal controls(P=0.039),and the lung adenocarcinoma raised the most obvious(P=0.007).The frequency of CD19+Fc?RIIbh,B cells in patients with lung cancer was associated with the degree of tumor infiltration(P=0.048),tumor stage(P=0.041)and metastasis(P=0.015),but not with age(P=0.191)and gender(P=0.536).[Conclusion]The average expression of Fc?RIIb in peripheral blood MDSCs of patients with lung cancer was significantly up-regulated compared with that of the normal controls,among which the most significant up-regulation was found in lung adenocarcinoma,and the average expression of Fc?RIIb in MDSCs was significantly correlated with TNM stage and lymph node metastasis.In addition,the frequency of CD19+Fc?RIIbhiB cells in peripheral blood of patients with lung cancer was correlated with tumor invasion,tumor TNM stage and whether accompanied by metastasis.The results above suggested that the average MFI of Fc?RIIb in MDSCs and the frequency of CD19+Fc?RIIbh,B cells in peripheral blood could be used as an effective evalution index for the detection of lung cancer progression. |
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