香菇多糖对新辅助化疗后乳腺癌患者免疫功能及淋巴细胞的影响
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摘要
目的探讨香菇多糖对新辅助化疗后乳腺癌患者免疫功能及淋巴细胞的影响。方法自2015年1月至2016年10月,前瞻性收集内蒙古医科大学附属医院收治的接受新辅助化疗的乳腺癌患者88例,采用随机对照的方式将其分为观察组(44例)和对照组(44例)。两组患者治疗方法相同,观察组联合应用香菇多糖,所有患者均新辅助化疗后手术切除肿瘤组织并留取肿瘤组织标本,观察肿瘤组织及外周血CD4+T细胞、CD8+T细胞、CD4+/CD8+比例以及血清白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、转化生长因子-β1(TGF-β1)浓度。结果治疗后,观察组肿瘤组织微环境CD4+T细胞明显低于对照组(21. 56%±5. 08%比23. 95%±5. 17%,t=2. 187,P=0. 031); CD8+T细胞高于对照组(29. 52%±3. 51%比27. 47%±3. 68%,t=2. 673,P=0. 009); CD4+/CD8+T细胞比例低于对照组(0. 72±0. 12比0. 86±0. 14,t=5. 036,P=0. 000)。外周血CD4+T细胞水平明显增加(28. 57%±4. 32%比26. 23%±4. 12%,t=2. 600,P=0. 011); CD4+/CD8+T细胞比例明显增加(0. 84±0. 15比0. 76±0. 13,t=2. 673,P=0. 009)。外周血IL-6浓度明显增高[(14. 56±4. 79)比(11. 45±4. 48) ng·L-1,t=3. 145,P=0. 002)]; IL-10浓度明显降低[(11. 34±3. 37)比(13. 46±3. 41) ng·L-1,t=2. 933,P=0. 004)]; TGF-β1浓度明显降低[(15. 14±4. 69)比(17. 67±4. 53)μg·L-1,t=2. 290,P=0. 024)]。结论香菇多糖有助于提高新辅助化疗后乳腺癌患者免疫功能,改善肿瘤组织微环境中免疫状态。
Objective To investigate the effect of lentinan on infiltrating lymphocytes in the microenvironment of breast cancer patients with neoadjuvant chemotherapy. Methods From January 2015 to October 2016,88 breast cancer patients admitted to our hospital received neoadjuvant chemotherapy and were randomly assigned into a study group(44 cases) and a control group(44 cases). Basic treatment were the same in two groups and patients in the study group received lentinan injection. After neoadjuvant chemotherapy,surgical resection were performed in all patients and tumor tissue were collected. The CD4+T cells,CD8+T cells and the proportion of CD4+/CD8+T cells in tumor tissue and peripheral blood and serum level of IL-6,IL-10 and TGF-β1 were observed. Results When compared with control group after the treatment,patients in the study group showed significantly decrease of CD4+T cells(21. 56 % ±5. 08 % vs. 23. 95% ± 5. 17%,t = 2. 187,P = 0. 031); increase of CD8+T cell(29. 52% ± 3. 51% vs. 27. 47% ± 3. 68%,t =2. 673,P = 0. 009) and decrease of the proportion of CD4+/CD8+T cells,respectively(0. 72 ± 0. 12 vs. 0. 86 ± 0. 14,t = 5. 036,P =0. 000). Moreover,in peripheral blood,patients in the study group got an elevated post-operative level of CD4+T cells(28. 57% ±4. 32% vs. 26. 23% ± 4. 12%,t = 2. 600,P = 0. 011),a higher level of CD4+/CD8+T(0. 84 ± 0. 15 vs. 0. 76 ± 0. 13,t = 2. 673,P =0. 009),an increase in IL-6 level(14. 56 ± 4. 79 vs. 11. 45 ± 4. 48 ng·L-1,t = 3. 145,P = 0. 002),a decrease in IL-10[(11. 34 ±3. 37) vs.(13. 46 ± 3. 41) ng·L-1,t = 2. 933,P = 0. 004) ],and a decrease in TGF-β1 [(15. 14 ± 4. 69) vs.(17. 67 ± 4. 53) μg·L-1,t = 2. 290,P = 0. 024) ]. Conclusions Lentinan is helpful to improve the immune status in the microenvironment and the total immune function in patients with breast cancer who underwent neoadjuvant chemotherapy.
Objective To investigate the effect of lentinan on infiltrating lymphocytes in the microenvironment of breast cancer patients with neoadjuvant chemotherapy. Methods From January 2015 to October 2016,88 breast cancer patients admitted to our hospital received neoadjuvant chemotherapy and were randomly assigned into a study group(44 cases) and a control group(44 cases). Basic treatment were the same in two groups and patients in the study group received lentinan injection. After neoadjuvant chemotherapy,surgical resection were performed in all patients and tumor tissue were collected. The CD4+T cells,CD8+T cells and the proportion of CD4+/CD8+T cells in tumor tissue and peripheral blood and serum level of IL-6,IL-10 and TGF-β1 were observed. Results When compared with control group after the treatment,patients in the study group showed significantly decrease of CD4+T cells(21. 56 % ±5. 08 % vs. 23. 95% ± 5. 17%,t = 2. 187,P = 0. 031); increase of CD8+T cell(29. 52% ± 3. 51% vs. 27. 47% ± 3. 68%,t =2. 673,P = 0. 009) and decrease of the proportion of CD4+/CD8+T cells,respectively(0. 72 ± 0. 12 vs. 0. 86 ± 0. 14,t = 5. 036,P =0. 000). Moreover,in peripheral blood,patients in the study group got an elevated post-operative level of CD4+T cells(28. 57% ±4. 32% vs. 26. 23% ± 4. 12%,t = 2. 600,P = 0. 011),a higher level of CD4+/CD8+T(0. 84 ± 0. 15 vs. 0. 76 ± 0. 13,t = 2. 673,P =0. 009),an increase in IL-6 level(14. 56 ± 4. 79 vs. 11. 45 ± 4. 48 ng·L-1,t = 3. 145,P = 0. 002),a decrease in IL-10[(11. 34 ±3. 37) vs.(13. 46 ± 3. 41) ng·L-1,t = 2. 933,P = 0. 004) ],and a decrease in TGF-β1 [(15. 14 ± 4. 69) vs.(17. 67 ± 4. 53) μg·L-1,t = 2. 290,P = 0. 024) ]. Conclusions Lentinan is helpful to improve the immune status in the microenvironment and the total immune function in patients with breast cancer who underwent neoadjuvant chemotherapy.
引文
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[14] FUJIOKA Y,NISHIKAWA H. Basics of cancer immunotherapy[J]. Rinsho Ketsueki,2016,57(11):2346-2354.
[15] JIANG S,YAN W. T-cell immunometabolism against cancer[J].Cancer Lett,2016,382(2):255-258.
[16]白海亚,马秀芬.新辅助化疗对局部进展期乳腺癌患者T淋巴细胞亚群及NK细胞免疫功能的影响[J].中国免疫学杂志,2012,28(9):843-845.
[17]张琪琳.香菇多糖的结构鉴定及抗肿瘤作用机制研究[D].武汉:华中科技大学,2015.
[18]向冬晴,洛若愚.香菇多糖对多西他赛联合顺铂治疗Ⅳ期宫颈癌疗效的影响[J].癌症进展,2016,08(7):808-810.
[19]龙爱娥.香菇多糖联合顺铂及紫杉醇治疗老年卵巢癌并腹水[J].临床医学,2016,6(5):5-8.
[20] HIRAHARA K,NAKAYAMA T. CD4+T-cell subsets in inflammatory diseases:beyond the Th1/Th2 paradigm[J]. Int Immunol,2016,28(4):163-171.
[21] WADWA M,KLOPFLEISCH R,ADAMCZYK A,et al. IL-10downregulates CXCR3 expression on Th1 cells and interferes with their migration to intestinal inflammatory sites[J]. Mucosal Immunol,2016,9(5):1263-1277.
[22] VARGAS-ROJAS MI,SOLLEIRO-VILLAVICENCIO H,SOTOVEGA E. Th1,Th2,Th17 and Treg levels in umbilical cord blood in preeclampsia[J]. J Matern Fetal Neonatal Med,2016,29(10):1642-1645.
[23] PEREZ-MAZLIAH D,LANGHORNE J. CD4 T-cell subsets in malaria:TH1/TH2 revisited[J]. Front Immunol,2014,5:671.
[24] FEYZI R,BOSKABADY MH,SEYEDHOSSEINI TAMIJANI SM,et al. The Effect of Safranal on Th1/Th2 Cytokine Balance[J]. Iran J Immunol,2016,13(4):263-273.
[25] KAJDANIUK D,MAREK B,BORGIEL-MAREK H. Transforming growth factorβ1(TGFβ1)in physiology and pathology[J]. Endokrynol Pol,2013,64(5):384-396.
[2] RAHMAN M,AHSAN A,BEGUM F,et al. Epidemiology,Risk Factors and Tumor Profiles of Breast Cancer in Bangladeshi underprivileged women[J]. Gulf J Oncolog,2015,1(17):34-42.
[3] KHAN AM,YUAN Y. Biopsy variability of lymphocytic infiltration in breast cancer subtypes and the ImmunoSkew score[J]. Sci Rep,2016,6:36231.
[4] KALBASI A,BEATTY GL,BERMAN AT. Expanding Tumor Lymphocytic Infiltration as a Prognostic Tool to Patients with NSCLC Who Are Treated with Radiotherapy?[J]. J Thorac Oncol,2016,11(11):e141-e142. DOI:10. 1016/j. jtho. 2016. 07. 029.
[5] BRAHA M,CHIKMAN B,HABLER L,et al. Lymphocytic Infiltration as a Prognostic Factor in Patients With Colon Cancer[J]. Int J Surg Pathol,2016,24(1):16-23.
[6] PLITAS G,KONOPACKI C,WU K,et al. Regulatory T Cells Exhibit Distinct Features in Human Breast Cancer[J]. Immunity,2016,45(5):1122-1134.
[7] FREIER CP,KUHN C,ENDRES S,et al. FOXP3+Cells Recruited by CCL22 into Breast Cancer Correlates with Less Tumor Nodal Infiltration[J]. Anticancer Res,2016,36(6):3139-3145.
[8] ASANO Y,KASHIWAGI S,GOTO W,et al. Tumour-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to neoadjuvant chemotherapy of aggressive breast cancer[J]. Br J Surg,2016,103(7):845-854.
[9] YIN X,YING J,LI L,et al. A meta-analysis of lentinan injection combined with chemotherapy in the treatment of nonsmall cell lung cancer[J]. Indian J Cancer,2015,52(Suppl 1):e29-e31.DOI:10. 4103/0019-509X. 168953.
[10] FANG J,XIAO L,JOO KI,et al. A potent immunotoxin targeting fibroblast activation protein for treatment of breast cancer in mice[J]. Int J Cancer,2016,138(4):1013-1023.
[11] GARCIA-TEIJIDO P,CABAL ML,FERNANDEZ IP,et al. TumorInfiltrating Lymphocytes in Triple Negative Breast Cancer:The Future of Immune Targeting[J]. Clin Med Insights Oncol,2016,10(Suppl 1):31-39.
[12] LEI J,RUDOLPH A,MOYSICH KB,et al. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility:a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium[J]. Hum Genet,2016,135(1):137-154.
[13] SPELLMAN A,TANG SC. Immunotherapy for breast cancer:past,present,and future[J]. Cancer Metastasis Rev,2016,22(3):219-223.
[14] FUJIOKA Y,NISHIKAWA H. Basics of cancer immunotherapy[J]. Rinsho Ketsueki,2016,57(11):2346-2354.
[15] JIANG S,YAN W. T-cell immunometabolism against cancer[J].Cancer Lett,2016,382(2):255-258.
[16]白海亚,马秀芬.新辅助化疗对局部进展期乳腺癌患者T淋巴细胞亚群及NK细胞免疫功能的影响[J].中国免疫学杂志,2012,28(9):843-845.
[17]张琪琳.香菇多糖的结构鉴定及抗肿瘤作用机制研究[D].武汉:华中科技大学,2015.
[18]向冬晴,洛若愚.香菇多糖对多西他赛联合顺铂治疗Ⅳ期宫颈癌疗效的影响[J].癌症进展,2016,08(7):808-810.
[19]龙爱娥.香菇多糖联合顺铂及紫杉醇治疗老年卵巢癌并腹水[J].临床医学,2016,6(5):5-8.
[20] HIRAHARA K,NAKAYAMA T. CD4+T-cell subsets in inflammatory diseases:beyond the Th1/Th2 paradigm[J]. Int Immunol,2016,28(4):163-171.
[21] WADWA M,KLOPFLEISCH R,ADAMCZYK A,et al. IL-10downregulates CXCR3 expression on Th1 cells and interferes with their migration to intestinal inflammatory sites[J]. Mucosal Immunol,2016,9(5):1263-1277.
[22] VARGAS-ROJAS MI,SOLLEIRO-VILLAVICENCIO H,SOTOVEGA E. Th1,Th2,Th17 and Treg levels in umbilical cord blood in preeclampsia[J]. J Matern Fetal Neonatal Med,2016,29(10):1642-1645.
[23] PEREZ-MAZLIAH D,LANGHORNE J. CD4 T-cell subsets in malaria:TH1/TH2 revisited[J]. Front Immunol,2014,5:671.
[24] FEYZI R,BOSKABADY MH,SEYEDHOSSEINI TAMIJANI SM,et al. The Effect of Safranal on Th1/Th2 Cytokine Balance[J]. Iran J Immunol,2016,13(4):263-273.
[25] KAJDANIUK D,MAREK B,BORGIEL-MAREK H. Transforming growth factorβ1(TGFβ1)in physiology and pathology[J]. Endokrynol Pol,2013,64(5):384-396.