Quantitative Multiplex Immunofluorescence Evaluation of the Tumor Microenvironment in Pretreatment Tumors of Patients with Metastatic Breast Cancer and Serous Ovarian Carcinoma Treated with Liposomal Eribulin

Abstract

Eribulin inhibits microtubule polymerization and suppresses epithelial-mesenchymal transition. Conventional pathology approaches have not identified a precise predictive biomarker for Eribulin. We performed qmIF on pre-treatment tissue from 11 patients (6 TNBC, 5 HGSOC) treated with Eribulin-LF. T-lymphocytes were the dominant immune-subset in TME, with higher levels detected in stroma vs tumor (9% vs 2%). Greater density of CD3+ (p = 0.01) and CD3 + CD8+ (p = 0.03) cells and closer proximity between CD3 + CD8+ and tumor cells was observed in the patients with disease control (PR + SD) vs. progressive disease. QmIF identified an association between TIL infiltration and Eribulin-LF sensitivity, which should be evaluated further in prospective studies.

Keywords:

• Metastatic breast cancer
• metastatic ovarian cancer
• EMT
• tumor microenvironment
• Eribulin-LF
• Eribulin
• quantitative multiplex immunofluorescence
• tumor immunobiology
• phase I clinical trial

Declaration of interest

The authors declare the following competing interests: Kevin Kalinsky (KK) has consultancy or advisory positions with bioTheranostics, Lilly, Pfizer, Amgen, Novartis, Eisai, AstraZeneca, Ipsen, Genentech/Roche, Immunomedics, Odonate Therapeutics, and immediate family member(s) with stock/ownership interest in Novartis and Array Biofarma. KK has also received fees to speak on behalf of Lilly. DM has had an advisory position with Seattle Genetics. The remaining co-authors declare no competing interests as it pertains to this study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. RDG is also supported by Swim Across America.

Additional information

Funding

This work was supported by Error! Hyperlink reference not valid.. In addition, this publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number [KL2 TR000081 (EC) and KL2TR001874 (RDG)]. This research was funded in part through the NIH/NCI Cancer Center Support Grant [P30CA013696], by virtue of the usage of the Molecular Pathology Shared Resource of the Herbert Irving Comprehensive Cancer Center of Columbia University.