The Prognostic Role of Tumor-Infiltrating Lymphocytes CD8 and Foxp3 and their Impact on Recurrence in Breast Cancer Patients

2016 ◽  
Vol 08 (07) ◽  
Author(s):  
Rasha Abd El-Ghany Khedr ◽  
Amr Abd El-Aziz Ghannam
2019 ◽  
Author(s):  
Morihito Okada ◽  
Noriko Goda ◽  
Shinsuke Sasada ◽  
Hideo Shigematsu ◽  
Norio Masumoto ◽  
...  

Abstract Background Tumor-infiltrating lymphocytes (TILs) in breast cancer comprise immunostimulating and immunosuppressive components. Although FOXP3+ TILs are prototypical immunosuppressive TILs, only effector regulatory T cells (eTreg), a subset of immunosuppressive FOXP3+ TILs, are undetectable on immunohistochemical staining. This study aimed to evaluate the immunosuppressive potential of eTregs and the role of prototypical immunostimulatory CD8+ TILs in invasive breast cancer. Methods Fresh TILs extracted from 84 invasive breast cancer patients were analyzed via flow cytometry. We evaluated eTregs (CD4+FOXP3highCD45RA−), other FOXP3+ Treg subsets (naïve and non-Tregs), and total CD8+CD4- TILs. Clinicopathological factors, including histopathological characteristics, were also assessed. Results The median eTreg proportion of the total CD4+TILs was 18.7% (interquartile range [IQR], 16.4–25.5%); CD8+TILs, 124% (IQR, 87.5–140%). The proportion of eTregs to total FOXP3+ TILs varied (median, 65.6%; range, 10.1–93.2%). In an immunosuppression assay, only eTregs displayed potent immunosuppression; however, other Treg subsets did not. Among 39 patients who received neoadjuvant chemotherapy, eTreg subsets and pathological compete response (pCR) did not differ significantly, while pCR rates were significantly higher among individuals with a high than those with a low CD8+/eTreg ratio (90.2% vs 33.3%; P<0.05). Among all patients, a high CD8+/eTreg ratio tended to be associated with better disease-free survival rather than a low CD8+/eTreg ratio (P=0.09). Conclusions The CD8+/eTreg ratio is simple, optimal indicator of cancer immunity, and a high CD8+/eTreg ratio enhances the prognosis and treatment response in invasive breast cancer patients. However, further studies are required to validate the present findings.


Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4656
Author(s):  
Christophe Van Berckelaer ◽  
Iris Vermeiren ◽  
Leonie Vercauteren ◽  
Charlotte Rypens ◽  
Gizem Oner ◽  
...  

Introduction: Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer (BC) in which the (prognostic) role of stromal tumour-infiltrating lymphocytes (sTIL) and the peripheral circulating immune cells in patients with residual disease (RD) after neo-adjuvant chemotherapy (NACT) is not clearly established. Methodology: To describe the evolution of sTIL and some peripheral inflammation markers (Neutrophil-to-lymphocyte ratio, Platelet-to-lymphocyte ratio and Lymphocyte-to-monocyte ratio) after NACT in IBC, we retrospectively collected clinicopathological variables for 125 stage III IBC patients. sTILs were scored by three different researchers on an H&E slide of the mastectomy specimen. A cohort of subtype-matched non-IBC breast cancer patients (nIBC) treated with NACT was included for comparison. Results: There was no significant difference in the pre- and posttreatment sTIL scores between IBC and nIBC and in both groups the number of sTIL was significantly lower after NACT. However, the IBC phenotype did correlate with a stronger decrease of sTIL after NACT (OR: 0.25, 95% CI: 0.073–0.76, p = 0.018). The change in the peripheral immune markers was not significantly different between IBC and nIBC. After NACT, 75 patients had residual disease. In this group, a high number of sTIL before NACT (HR: 0.23, 95% CI: 0.05–1.02, p = 0.05) was prognostic for a longer OS, while a low number of sTIL after NACT (HR: 0.33, 95% CI: 0.11–0.98, p = 0.046) and a low residual cancer cellularity (HR: 0.20, 95% CI: 0.08–0.52, p < 0.001) was associated with a longer DFS. Conclusions: IBC is associated with a significantly stronger decrease of sTIL after NACT compared to nIBC. Furthermore, a high number of sTIL after NACT was associated with a worse prognosis in IBC.


2020 ◽  
Vol 23 (2) ◽  
pp. 182 ◽  
Author(s):  
Yaewon Yang ◽  
Ahrum Min ◽  
Kyung-Hun Lee ◽  
Han Suk Ryu ◽  
Tae-Yong Kim ◽  
...  

2019 ◽  
Vol 51 (1) ◽  
pp. 128-140 ◽  
Author(s):  
Ling Deng ◽  
Xuehua Zhu ◽  
Yun Sun ◽  
Jiemin Wang ◽  
Xiaorong Zhong ◽  
...  

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 536-536
Author(s):  
Christian F. Singer ◽  
Stephan W Jahn ◽  
Margaretha Rudas ◽  
Zsuzsanna Bago-Horvath ◽  
Florian Fitzal ◽  
...  

536 Background: We have recently demonstrated that urokinase Plasminogen Activator (uPA), together with its inhibitor PAI-1, have prognostic value in hormone-receptor positive early breast cancer, and can be measured in FFPE archived tumor samples. We have now aimed to validate the prognostic role of uPA protein expression in FFPE archived tumor samples in an independent cohort of endocrine-treated breast cancer patients. Methods: 303 postmenopausal women with hormone receptor–positive, early breast cancer who had received 5 years of endocrine therapy in the prospectively designed ABCSG-08 trial, and in whom FFPE tumor tissue was available, were included in this analysis. Stromal uPA and PAI-1 protein expression was evaluated by immunohistochemistry and correlated with distant recurrence-free survival (DRFS) and overall survival (OS). Results: Stromal uPA was detected in 132 of 297 tumors (44.4%), and 74 out of 269 samples (27.5%) exhibited stromal PAI-1, while co-expression of both proteins was found in 48 of 294 (16.3%) samples. Neither uPA nor PAI-1 expression were associated with tumor size, age, nodal status, grading, or receptor status. Patients whose tumor stroma expressed uPA protein were more likely to have a shorter DRFS (adjusted HR for relapse: 2.78; 95% CI 1.31-5.93; p=0.008 Cox regression analysis) and OS (adjusted HR for death: 1.29; 95% CI 0.86-12.50; p=0.161) than women without uPA expression. No such association was observed for PAI-1 and for the uPA/PAI1 ratio. After a median follow-up of 5.6 years women with uPA-positive tumors experienced a significantly shorter DRFS (93.3% vs 84.8%; p<0.013 log rank test) and tended to have a worse OS (83.0.4% vs 77.3%; p=0.106) compared to women with uPA negative tumors. Conclusions: By confirming the clinical utility of stromal uPA IHC in archived breast cancer samples from an independent prospective randomized trial, we now provide level 1b evidence for a prognostic role of stromal uPA in women with endocrine-responsive early breast cancer.


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