骨髓来源抑制细胞在非小细胞肺癌患者治疗中的变化及其意义
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摘要
背景和目的
肺癌是目前世界发病率最高的肿瘤,尤其在我国,近年来发病率急剧升高。目前,肺癌的治疗还是以手术,放化疗为主,近些年以EGFR-TKI为主的靶向治疗在非小细胞肺癌中取得了重大突破。肺癌本身恶性程度高,治疗预后不佳。骨髓来源抑制细胞(MDSC)是一组具有高度异质性的细胞群,它可在肿瘤、炎症、感染等疾病中异常升高,并具有显著的抑制T细胞的功能。MDSC可介导肿瘤细胞产生免疫耐受,并成为免疫治疗的重大障碍。目前已在多种肿瘤中发现MDSC的异常聚集,并发现MDSC水平与部分肿瘤患者的预后有关,但MDSC在非小细胞肺癌中的研究还相当匮乏。
本实验主要研究MDSC在非小细胞肺癌患者治疗前后的变化及其与临床特征、CRP关系,以了解检测MDSC在非小细胞肺癌患者治疗中的意义。
方法
采取目标患者治疗前后的外周血,通过流式细胞学,计算外周血中MDSC占白细胞的比例,并同时检测患者外周血CRP水平。
结果
1.非小细胞肺癌患者外周血MDSC水平高于健康对照组,差别有统计学意义(P0.05)。
2. ⅢⅣ期非小细胞肺癌患者其外周血MDSC水平要高于ⅠⅡ期患者,差别有统计学意义(P 3.无论治疗前和治疗后,患者外周血MDSC水平与血清CPR水平均成正相关。
4.手术治疗患者其术后外周血MDSC水平低于术前(P<0.05)。但术后高CRP组患者其术后MDSC水平与术前无明显变化；术后低CRP组其术后MDSC水平明显低于术前(P<0.05)。
5.PR组患者化疗后MDSC水平较化疗前降低(P<0.05)。 SD、PD组患者化疗前后MDSC水平无明显变化。
结论
1.非小细胞肺癌患者外周血MDSC水平异常增高,提示患者处于免疫抑制状态。
2.手术切除和有效的化疗可降低非小细胞肺癌的MDSC水平。
3.非小细胞肺癌患者的MDSC水平与CRP水平呈正相关,CRP水平可作为评估患者免疫抑制状态的指标。
4.非小细胞肺癌患者的MDSC的水平可能与预后不良有关。
Background and Objectives
Lung cancer is the disease which has the highest incidence in human cancer in the world.especially in China, the incidence of lung cancer become higher and higher in recent years. Surgery, radiotherapy and chemotherapy are the major measure of therapy in lung cancer. Recently, targeted therapy with ERGR-TKI in non-small cell lung cancer acquires huge progress. Lung cancer has high grade malignancy and poor prognosis. Myeloid derived suppressor cells(MDSCs)are a heterogeneous population of cells that expands during cancer, inflammation and infection,and that has a remarkable ability to suppress T-cell responses. MDSC can induce immune tolerance in the development of tumor cell, and is an obstacle in immune therapy. MDSC accumulate in many kinds of cancer, and relates to prognosis in some cancer. But, studies of MDSC is still limited in non-small cell lung cancer patients.
To explore the change of MDSC during the therapy in non-small cell lung cancer patients. Analyzing the relationship between MDSC, clinical character and C-reactive protein. Thereby, realizing the significance of MDSC C in non-small cell lung cancer patients.
Methods
The population of CDllb+CD33+cells in peripheral blood leucocytes was determined by Flow Cytometer in129patients with NSCLC and30control subjects. Peripheral blood C-reactive protein was determined as well.
Results
1. there is higer level of peripheral blood MDSC in NSCLC patients than in healthy person. The differences between the two groups were statistical signifaicance(P<0.05)
2. Patients with ⅢⅣ stage have higher level of peripheral blood MDSC than patients with ⅠⅡ stage(P<0.05). And the level of peripheral blood MDSC was irrelevant to the age, sex and histology types.
3. The level of peripheral blood MDSC and CRP have positive correlation whatever before or after therapy.
4. After remove of tumor,the level of peripheral blood MDSC was reduced in the NSCLC patients(P<0.05). But it is no obvious change in patients who have high level of CRP after surgery. And it is sharp reduced in the patients who have low level of CRP after surgery(P<0.05).
5. The level of peripheral blood MDSC is reduced in the NSCLC patients who receive PR to the chemotherapy(P<0.05). And it is no obvious change in patients who receive SD or PD to chemotherapy.
Conclusion
1. There is higher level of peripheral blood MDSC in NSCLC patients than in healthy person
2. The. level of peripheral blood MDSC is reduced in the NSCLC patients who had responsiveness to chemotherapy and after removal of tumor.
3. The level of peripheral blood MDSC and CRP have positive correlation.
4. High level of peripheral blood MDSC may imply poor prognosis.
肺癌是目前世界发病率最高的肿瘤,尤其在我国,近年来发病率急剧升高。目前,肺癌的治疗还是以手术,放化疗为主,近些年以EGFR-TKI为主的靶向治疗在非小细胞肺癌中取得了重大突破。肺癌本身恶性程度高,治疗预后不佳。骨髓来源抑制细胞(MDSC)是一组具有高度异质性的细胞群,它可在肿瘤、炎症、感染等疾病中异常升高,并具有显著的抑制T细胞的功能。MDSC可介导肿瘤细胞产生免疫耐受,并成为免疫治疗的重大障碍。目前已在多种肿瘤中发现MDSC的异常聚集,并发现MDSC水平与部分肿瘤患者的预后有关,但MDSC在非小细胞肺癌中的研究还相当匮乏。
本实验主要研究MDSC在非小细胞肺癌患者治疗前后的变化及其与临床特征、CRP关系,以了解检测MDSC在非小细胞肺癌患者治疗中的意义。
方法
采取目标患者治疗前后的外周血,通过流式细胞学,计算外周血中MDSC占白细胞的比例,并同时检测患者外周血CRP水平。
结果
1.非小细胞肺癌患者外周血MDSC水平高于健康对照组,差别有统计学意义(P0.05)。
2. ⅢⅣ期非小细胞肺癌患者其外周血MDSC水平要高于ⅠⅡ期患者,差别有统计学意义(P
4.手术治疗患者其术后外周血MDSC水平低于术前(P<0.05)。但术后高CRP组患者其术后MDSC水平与术前无明显变化；术后低CRP组其术后MDSC水平明显低于术前(P<0.05)。
5.PR组患者化疗后MDSC水平较化疗前降低(P<0.05)。 SD、PD组患者化疗前后MDSC水平无明显变化。
结论
1.非小细胞肺癌患者外周血MDSC水平异常增高,提示患者处于免疫抑制状态。
2.手术切除和有效的化疗可降低非小细胞肺癌的MDSC水平。
3.非小细胞肺癌患者的MDSC水平与CRP水平呈正相关,CRP水平可作为评估患者免疫抑制状态的指标。
4.非小细胞肺癌患者的MDSC的水平可能与预后不良有关。
Background and Objectives
Lung cancer is the disease which has the highest incidence in human cancer in the world.especially in China, the incidence of lung cancer become higher and higher in recent years. Surgery, radiotherapy and chemotherapy are the major measure of therapy in lung cancer. Recently, targeted therapy with ERGR-TKI in non-small cell lung cancer acquires huge progress. Lung cancer has high grade malignancy and poor prognosis. Myeloid derived suppressor cells(MDSCs)are a heterogeneous population of cells that expands during cancer, inflammation and infection,and that has a remarkable ability to suppress T-cell responses. MDSC can induce immune tolerance in the development of tumor cell, and is an obstacle in immune therapy. MDSC accumulate in many kinds of cancer, and relates to prognosis in some cancer. But, studies of MDSC is still limited in non-small cell lung cancer patients.
To explore the change of MDSC during the therapy in non-small cell lung cancer patients. Analyzing the relationship between MDSC, clinical character and C-reactive protein. Thereby, realizing the significance of MDSC C in non-small cell lung cancer patients.
Methods
The population of CDllb+CD33+cells in peripheral blood leucocytes was determined by Flow Cytometer in129patients with NSCLC and30control subjects. Peripheral blood C-reactive protein was determined as well.
Results
1. there is higer level of peripheral blood MDSC in NSCLC patients than in healthy person. The differences between the two groups were statistical signifaicance(P<0.05)
2. Patients with ⅢⅣ stage have higher level of peripheral blood MDSC than patients with ⅠⅡ stage(P<0.05). And the level of peripheral blood MDSC was irrelevant to the age, sex and histology types.
3. The level of peripheral blood MDSC and CRP have positive correlation whatever before or after therapy.
4. After remove of tumor,the level of peripheral blood MDSC was reduced in the NSCLC patients(P<0.05). But it is no obvious change in patients who have high level of CRP after surgery. And it is sharp reduced in the patients who have low level of CRP after surgery(P<0.05).
5. The level of peripheral blood MDSC is reduced in the NSCLC patients who receive PR to the chemotherapy(P<0.05). And it is no obvious change in patients who receive SD or PD to chemotherapy.
Conclusion
1. There is higher level of peripheral blood MDSC in NSCLC patients than in healthy person
2. The. level of peripheral blood MDSC is reduced in the NSCLC patients who had responsiveness to chemotherapy and after removal of tumor.
3. The level of peripheral blood MDSC and CRP have positive correlation.
4. High level of peripheral blood MDSC may imply poor prognosis.
引文
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