Use of Tumor-infiltrating lymphocytes (TILs) to predict the treatment response to eribulin chemotherapy in breast cancer

Abstract

BackgroundEribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker.MethodsTILs was evaluated in 52 patients with MBC who underwent chemotherapy with eribulin. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of eribulin chemotherapy, was investigated retrospectively.ResultsOf the 52 MBC patients, 29 (55.8%) were in the high TILs group and 23 (44.2%) were in the low TILs group. The high TILs group included significantly more triple-negative breast cancer (TNBC) (p = 0.008) than the low TILs group. In an analysis of outcomes, TNBC patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank). In a multivariate analysis of recurrence in TNBC patients, being in the high TILs group was again an independent factor for a good outcome (p = 0.031, HR = 0.063).ConclusionThe results of this study suggest that TILs may be useful as a predictive marker of the therapeutic effect of eribulin chemotherapy in TNBC.

Eribulin Promotes Antitumor Immune Responses in Patients with Locally Advanced or Metastatic Breast Cancer

“…In this manner, EMT also ANTICANCER RESEARCH 38: 2929-2938(2018 2934 regulated immune functions in tumor tissues. We have previously reported that the number of tumor-infiltrating lymphocytes is a predictive marker for eribulin-responders (33). Our updated results indicate that eribulin accelerated the anti-tumor immune response and also showed efficacy in patients with metastatic breast cancer.…”

Utility of the Absolute Lymphocyte Count and Neutrophil/Lymphocyte Ratio for Predicting Survival in Patients with Metastatic Breast Cancer on Eribulin: A Real-World Observational Study

“…Although no significant difference in OS was observed between groups with high and low ALC (c; p = 0.287), those with NLR ≥5.0 had significantly worse OS than those with NLR < 5.0 (d; p < 0.001). antitumor immunity [7,8], while the number of tumorinfiltrating lymphocytes has been known to affect the efficacy of eribulin treatment for breast cancer [23]. Given the difficulty in determining the number of tumor-infiltrating lymphocytes in daily practice, we propose the use of ALC as a predictive marker of the efficacy of eribulin, considering that a significant correlation between tumor-infiltrating lymphocytes and ALC has been already confirmed [18].…”

MORAb-202, an Antibody–Drug Conjugate Utilizing Humanized Anti-human FRα Farletuzumab and the Microtubule-targeting Agent Eribulin, has Potent Antitumor Activity

“…Eribulin presents a unique opportunity to investigate a compound that has a number of beneficial nonmitotic properties, in addition to its potent antimitotic properties, as an ADC payload. Eribulin has been shown to inhibit epithelial-to-mesenchymal transition (EMT), which has been associated with a more immunosuppressive tumor microenvironment (19,20), and enhance infiltration of tumor-infiltrating lymphocytes (47). In addition, eribulin also increases vascular perfusion in tumors and reduces hypoxia.…”