| BackgroundTriple Negative Breast Cancer(TNBC)is a highly heterogeneous,aggressive disease with a high risk of recurrence and metastasis.Due to insensitivity to endocrine therapy and targeted HER2 therapy,the treatment for TNBC is relatively limited.Chemotherapy based on anthracyclines and platinum in combination with taxane is one of the standard treatments in TNBC.However,the resistance to chemotherapy can lead to tumor recurrence and metastasis.Therefore,the exploration of new therapeutic targets and tools for TNBC is of great significance.Recently,the immunotherapy based on immune checkpoint inhibitors provides a new idea for TNBC treatment.Immune checkpoints is a series of key protective molecules that regulate the activation o f T cells Immune checkpoint is a series of key protective molecules that regulate the activation of T cells.In contrast,over-expressing immune checkpoint in tumor tissues leads to escaping immune surveillance and promoting self-proliferation.Cytotoxic T lymphocyte-associated protein 4(CTLA-4)is one of the hottest topics in immune checkpoint research.CTLA-4 is a T-cell transmembrane leukocyte differentiation antigen that binds B7 competitively with CD28 and participates in the negative regulation of the immune response.It is now widely accepted that CTLA-4 is a molecule that plays inhibitory role in the activation of T cells.Blocking CTLA-4 can inhibit the proliferation of Foxp3+ regulatory T cells and AKT phosphorylation in the tumor microenvironment,which induces cytotoxic T cell activation,and enhances the anti-tumor effects.The efficacy of CTLA-4antibodies has now been demonstrated in a variety of advanced tumors,including non-small cell lung cancer,melanoma,and kidney cancer.It is found that patients with high CTLA-4 expression tend to be more sensitive to immunotherapy in melanoma,indicating that CTLA-4 expression is a predictive factor for efficiency of immunotherapy.Therefore,to explore the correlation between CTLA-4 expression and clinicopathological characteristics of TNBC may provide a new indicator for the prognosis of TNBC.ObjectiveTo investigate the correlation between the CTLA-4 expression and the clinicopathological features of TNBC.To analyze whether the expression of CTLA-4 in TNBC patients can be a prognostic indicator for TNBC,and provide a new biomarker for TNBC prognosis.MethodsWe collected 123 tissue microarrays from patients with complete survival follow-up information and clinicopathological data.The characteristics included T stage,N stage,survival status,age,pathological stage,type of pathology,histological type,ki67 expression,menopausal status,and so on.The chi-square and Fisher’s exact test were used to analyze the correlation between CTLA-4expression and clinicopathological factors in TNBC.The Kaplan-Meier survival analysis was applied for survival curves.Independent prognostic factors were identified by COX proportional hazards model.The prognostic nomogram was developed based on the multivariate analysis,and the accuracy and effectiveness of the nomogram were evaluated.Results(1)CTLA-4 expression in TNBC was positively correlated with age(p < 0.05),but not related to tumor T-stage,N-stage,Ki67 expression,or menstrual status(p > 0.05)(2)CTLA-4 expression was associated with the prognosis of TNBC,and high expression of CTLA-4 in TNBC had a worse overall survival(p < 0.05).(3)CTLA-4 over-expression was related to 3-year and 5-year overall survival.Conclusions(1)Age is an influential factor in CTLA-4 expression level.(2)CTLA-4 could be an independent prognostic predictor in TNBC.(3)CTLA-4 expression level,pathological stage,and axillary lymph node metastasis are independent OS factors in TNBC patients.(4)A prognostic nomogram based on CTLA-4 expression and clinicopathological factors is investigated to be a personalized tool for predicting the prognosis of TNBC patients. |
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