Effect Of Chemotherapy On The Ratio Of MDSCs And Lymphocytes In Reconstituted Mouse Mammary Tumors

Currently,surgical excision combined with chemotherapy is the preferred treatment for most breast cancer patients.Studies have shown that combination of immunotherapy can significantly improve the therapeutic effect,but immunosuppression is a major obstacle to the effectiveness of immunotherapy.Immune cells have a monitoring and scavenging effect on tumors and can kill tumor cells directly or indirectly.Myelosuppressive cells can inhibit T immune function and immature myelogenous immune cells,including dendritic cells,granuLocytes,macrophages and so on.Some studies have shown that MDSCs play an important role in the immune escape of tumor cells,and the proportion of MDSCs is highly correlated with tumor resistance and recurrence rate.Therefore,to clarify the dynamic changes of immune cell subsets in the course of chemotherapy can provide ideas for the combination of chemotherapy and immunotherapy.This study used a highly metastatic 4T1mouse breast cancer model to explore the relationship between the ratio of MDSC and lymphocytes in the process of tumor cell death after chemotherapy and chemotherapy by flow cytometry with the neoadjuvant chemotherapy(NACT)regimen(docetaxel+pirarubicin+cyclophosphamide)at different stages after cancer(early,mid-term,and late).At the same time,physiological indicators such as tumor growth curve,food and water intake,and body weight were recorded.The resuLts showed that in the different periods of chemotherapy,7 days after transplantation(early),when the tumor volume was 32.1±5.3 mm3,the in situ tumors were completely eliminated after administration;At 14 days after transplantation,when the tumor volume was 61±15.8 mm~3,the tumor volume continued to decrease after chemotherapy.At21 days after transplantation,when the volume of the tumor was 108±18.3 mm~3,the growth rate of the tumor couLd be significantly inhibited after chemotherapy.In spleen tissues,the proportion of CD3~+T cells after early,middle and late chemotherapy was significantly higher than that of the transplanted control group(50.85±7.0%vs.17.2±2.1%,p<0.01;72.7±10.0%vs.17.2±2.1%,p<0.01;66.95±9.5%vs.17.2±2.1%,p<0.01),while the proportion of MDSCs was lower than that in transplantation control group(28.4±4.5%vs.35.5±4.1%,p>0.05;4.7±1.1%vs.35.5±4.1%,p<0.01;5.4±1.0%±9.5%vs.35.5±4.1%,p<0.01).At different time points after chemotherapy,the proportion of MDSC cells in the spleen was significantly higher than that in the 4T1 control group at 7 days after administration(42.5±4.1%vs.27.6±2.9%,p<0.01),and the proportion of NKp46~+cells was lower than that of 4T1 control group(1.2±0.2%vs.2.1±0.1%,P<0.05).At 14 days after chemotherapy,the proportion of MDSCs in spleen was significantly higher than that in 4T1 control group(37.4±3.4%vs.29.7±3.1%,p<0.01),and the proportion of CD3~+T cells and CD8a~+T cells was higher than that in 4T1control group(30.3±2.3%vs.24.5±1.0%,P<0.05;41.5±3.3%vs.29.2±2.6%,P<0.05).At 21 days after chemotherapy,the proportion of MDSCs in spleen was significantly lower than that in 4T1 control group and 14 days after chemotherapy(17.5±2.1%vs.33.6±2.9%,p<0.01;17.5±2.1%vs.37.4±4.1%,p<0.01),but still higher than that in healthy control group(17.5±2.1%vs.2.19±0.6%,p<0.01).The proportion of CD3~+T and NKp46~+cells in spleen was higher than that in 4T1 control group(25.7±2.8%vs.14.5±1.3%,P<0.05;3.9±0.3%vs.0.9±0.2%,P<0.01).At the beginning of chemotherapy,the mice's diet and drinking water decreased significantly,reaching the lowest level after 4 days of chemotherapy(2.1±0.85 g),gradually returning to the normal level after 14 days of chemotherapy(7.9±1.2 g),The body weight of mice decreased continuously,and the biggest decrease was achieved when the normal diet and water intake was restored(16.5%-21.3%of the body weight).The resuLts suggest that the TAC treatment regimen can effectively eliminate orthotopic tumors?61±15.8 mm~3,and effectively inhibit the proliferation of orthotopic tumors of108±18.3 mm~3.At the initial stage of administration,it has strong toxic side effects on lymphocytes,and gradually reduces the side effects of lymphocytes over time,and can significantly reduce the proportion of MDSC cells in tumor-bearing mice under the premise of effectively controlling tumor proliferation.Combining the three tissues in this experiment,it is preliminarily obtained that chemotherapy begins when the diameter of the tumor is 5-8mm3,the proportion of immune cells increases most significantly 21 days after chemotherapy,and the proportion of MDSC cells decreases most significantly.At this time,the effect of immune therapy is better.