Study On The Correlation Between Myeloid Derived Suppressor Cells And Regulatory T Cells In Breast Cancer And Their Clinical Significance

Objective:Myeloid derived suppressor cells (MDSCs) in the tumor microenvironment is important inhibitory immune cells directly involved in tumor immune escape and metastasis. This experimental intended to study the distribution of myeloid derived suppressor cells (CD33+ MDSCs) and regulatory T cells (Foxp3+ Tregs) in various stages of breast cancer tissue, detect the protein expression of STAT3 and IDO in MDSCs, analysis the correlation between Foxp3+Tregs, CD33+MDSCs and STAT3+IDO+MDSCs in all breast carcinoma samples, and study the relationship between the distribution of these two cell subsets and clinical information.Methods:50 cases of paraffin-embedded breast cancer samples of patients who received surgery in January 2005 in Tianjin Medical University Cancer Hospital were collected for this study. The distribution of myeloid derived suppressor cells (CD33+ MDSCs) and regulatory T cells (Foxp3+ Tregs) in various stages of breast cancer tissue were evaluated by immunohistochemical staining method. The protein expression and cell location of CD33 and Foxp3 was detected using the single-dye IHC method, and the expression of STAT3 and IDO in the MDSCs was detected using the double-dye IHC method. The correlation between Foxp3+Tregs, CD33+MDSCs and STAT3+IDO+MDSCs in all breast carcinoma samples, and the relationship between the distribution of these two cell subsets and clinical information were analyzed.Results:1. Foxp3 protein located in the nucleus, mainly expressed in breast cancer nest among the infiltrating lymphocytes while few expessed in some breast cancer cells also. CD33 cell located in membrane, a small amount cell of expression is also in pulp, most expressed in the cancer nest between the normal cells, the nucleus can be seen MDSC larger kidney-shaped and horseshoe-shaped, abundant cytoplasm, irregular cell shape, showing a myeloid progenitor cell morphology.IDO most expressed in breast cancer cells, located in the cytoplasm of cancer nests between normal cells as well as some expression. STAT3 mainly in breast cancer tissues, localized in the cytoplasm and nucleus, at the same time the quality of normal cells also expressed, but also a small amount present in normal breast tissues such as breast epithelial cells2.Immunohistochemistry showed that in all breast cancer samples, the rate in the group with high proportion of Foxp3+Tregs was 60%(30/50), in the group with low proportion and negative of Foxp3+Tregs was 40%(20/50),in breast cancer,the Foxp3+Tregs expression level are closely related with axillary lymph node metastasis and C-erbB-2 overexpression(P<0.05).3.Immunohistochemistry double staining showed that in all breast cancer samples,the CD33+MDSCs detection rate was 64%(32/50),and the detection rate of MDSCs with STAT3 and IDO expression simultaneously (STAT3+IDO+MDSCs) was 52%(26/50). The STAT3+IDO+MDSCs expression level was closely related with axillary lymph node metastasis (P<0.05).4. In the group with high proportion of Foxp3+Tregs, the positive rates of CD33+MDSCs and STAT3+IDO+MDSCs were 86.7%(26/30),66.7%(20/30) respectively. In the group with low proportion and negative of Foxp3+Tregs,the positive rates both were 30%(6/20). Therefore, the two expression rates in the group with high proportion of Foxp3+Tregs was higher than the group with low proportion and negative, and there was statistically significant (P<0.05).5. The 3 and 5 years disease-free survival rate in the group with high proportion of Foxp3+Tregs in breast cancer patients were less than the group with low proportion and negative, they were 100%(20/20) and 86.7%(26/30),95%(19/20) and 80% (24/30) respectively.And The 3 and 5 years disease-free survival rate in STAT3+IDO+MDSCs double-positive group of patients were less than a single positive and double negative group,they were 95.8%(23/24) and 88.5%(23/26), 87.5%(21/24) and 84.6%(22/26) respectively, but the differences were not statistically significant(P>0.05).Conclusion:1. The Foxp3+Tregs expression level are closely related with axillarylymph node metastasis and C-erbB-2 overexpression,the STAT3+IDO+MDSCs expression level was closely related with axillary lymph node metastasis in the breast cancer. The 3 and 5 years disease-free survival rate in the group with high proportion of Foxp3+Tregs in breast cancer patients were less than the group with low proportion and negative.The 3 and 5 years disease-free survival rate in STAT3+IDO+MDSCs double-positive group of patients less than a single positive and double negative group. These results implied that Foxp3+Tregs and STAT3+IDO+MDSCs may benefit to promote the development of breast cancer.2. In the group with high proportion of Foxp3+Tregs in breast cancer patients, the detection rate of the CD33+MDSCs and STAT3+IDO+MDSCs was higher than the the group with low proportion and negative.These results implied that increased proportion of MDSCs might favor the increase of Tregs. The abnormal activation of STAT3 in MDSCs may induce amplification of Tregs by increasing expression of IDO which gave help to development of the local immunosuppressive microenvironment and further promote aggression and metastatis of breast cancer.