| BackgroundTriple-negative breast cancers(TNBC)were a special phenotype of breast cancer subtype with rapid disease progression,early visceral metastasis,and low survival rate.At present,there is still no treatment guideline for TNBC,and more reference is given to the treatment of non-three-negative breast cancer,including surgical treatment,radiotherapy,chemotherapy,etc.The number of tumor infiltrating CD8~+T cells was regulated by T cell immunoglobulin and mucin-domain containing molecules family-3(TIM-3)Tim-3.Once CD8~+T cells express co-inhibitory molecules such as Tim-3 and PD-1,the number of CD8~+T cells will decrease,and the prognosis of patients will be worse.In addition,TIM-3 is expressed in a variety of tumor tissues,and the higher the level of TIM-3,the worse the prognosis of patients.Therefore,studying the expression of TIM-3 in tumor-infiltrating CD8~+T cells in TNBC is of great significance for finding potential new independent prognostic indicators and therapeutic targets for triple-negative breast cancer.ObjectiveBy examining the expression of CD8~+T and TIM-3 in the TNBC and the NTNBC groups,the relationship between clinicopathological features and prognosis was analyzed.The expression of TIM-3 on tumor-infiltrating CD8~+T cells was detected by fluorescent double staining to further understanding the relationship between TIM-3 regulation of immune microenvironment and tumor prognosis in TNBC.And learn more about whether TIM-3 is one of the potential new independent prognostic indicators and the therapeutic targets in TNBC.MethodsFrom January 2012 to December 2014,40 patients with TNBC who were admitted to the department of general surgery in the First Hospital of Longyan of the Affiliated Hospital of Fujian Medical University,was selected as the study group.In the control group,120 NTNBC patients and 40 breast fibroadenomas and40 paracancerous tissues were selected(including 10 cases of TNBC and 30 cases of NTNBC,which were obtained from normal tissues 5 cm away from the tumor edge).1.Statistical analysis of clinical data of each case,including the age,the clinical stage,the size of tumor,and the axillary lymph node metastasis and so on.2.The expression of CD8~+T and TIM-3 in tumor tissue in the paraffin specimens of the study group and the control group were detected by immunohistochemistry.The relationship between the expression difference and clinicopathological features was statistically analyzed.3.Immunofluorescence double staining was used to detect the expression of CD8~+T strong positive expression in tumor infiltration,and the co-expression of TIM-3 and CD8 was observed.The relationship between the regulation of Tim-3on immune microenvironment in TNBC and malignant degree of tumor was analyzedResults1.In the TNBC group,the composition ratios of<45 years old,high Ki-67expression,histological grade III,lymph node metastasis positive,survival rate and other factors were significantly higher than those of NTNBC group,and the difference was statistically significant(P<0.05).2.The positive expression rates of tumor infiltration CD8~+T and TIM-3 in TNBC group and NTNBC group were significantly higher than those in control breast fibroadenoma group(P<0.05).The positive expression rate of tumor-infiltrating CD8~+T cells in the TNBC group was higher when the WHO classification was lower and the tumor-free survival rate was large(P<0.05).However,it was not related to the molecular typing,Ki-67 and clinical stage of the patients(P>0.05).The positive expression rate of Tim-3 in both the TNBC group and the NTNBC group was higher when axillary lymph node metastasis,late clinical staging,and high recurrence or metastasis rate(P<0.05).The positive rate of high expression of TIM-3 in Ki-67 of the TNBC group was larger(P<0.05).3.The positive expression rates of TIM-3 and tumor-infiltrating CD8~+T of immunofluorescence co-expression were significantly higher in the TNBC group than in the NTNBC group and the adenocarcinoma group.(P<0.05).The positive expression rate of TIM-3 and tumor-infiltrating CD8~+T cells in the TNBC group was higher when Ki-67 was higher and WHO classification was higher.Conclusion1.Compared with NTNBC patients,TNBC patients have clinical characteristics such as early onset age,high histological grade,prone to lymph node metastasis,and poor prognosis.2.CD8~+T cells and TIM-3 are highly expressed in breast cancer.When the degree of malignancy of TNBC was low,the positive expression rate of CD8~+T cells was higher,while the degree of malignancy of NTNBC was not significantly correlated with the positive expression rate of CD8~+T cells.The positive expression rate of TIM-3 was higher when the malignancy of breast cancer was higher.At the same time,their level of expression is closely related to the axillary lymph node metastasis,pathological stage,and degree of differentiation of breast cancer.The positive expression of TIM-3 was positively correlated with the expression of KI-67 in the TNBC group,but there was no significant difference in the NTNBC group,indicating that TIM-3 may promote tumor proliferation,development or metastasis in TNBC,leading to poor prognosis and high mortality.3.When the malignant degree of triple-negative breast cancer is high,the co-expression rate of TIM-3 and CD8~+T cells is high.The results of co-expression were consistent with the high positive expression rate of TIM-3 in the high degree of malignancy of breast cancer,but not the similarity of CD8~+T cells in the low degree of malignancy of breast cancer.Therefore,we believe that the expression of CD8~+T cells in poor cases of TNBC still suggests a poor prognosis,which may be closely related to the co-expression of TIM-3 and CD8~+T cells.TIM-3 plays a negative regulatory role in the immune regulation of TNBC,and TIM-3 has an inhibitory effect on the function of CD8~+T cells.4.TIM-3 plays a negative regulatory role in the immune regulation of breast cancer.TIM-3 may be an emerging therapeutic target or potential independent prognostic factor for TNBC. |
PDF Full Text Request