Wataru Goto1, Shinichiro Kashiwagi2, Yuka Asano1, Koji Takada1, Tamami Morisaki1, Hisakazu Fujita3, Tsutomu Takashima1, Masahiko Ohsawa4, Kosei Hirakawa1, Masaichi Ohira1. 1. Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan. 2. Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan spqv9ke9@view.ocn.ne.jp. 3. Department of Scientific and Linguistic Fundamentals of Nursing, Osaka City University Graduate School of Nursing, Osaka, Japan. 4. Department of Diagnostic Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Abstract
BACKGROUND/AIM: Several proteins involved in immune regulation and the relationship among these, the tumor microenvironment, and clinical outcomes of eribulin treatment were evaluated in advanced or metastatic breast cancer patients. PATIENTS AND METHODS: This retrospective cohort study comprised 52 eribulin-treated locally advanced or metastatic breast cancer patients. Cancer tissue samples were obtained before and after treatment in 10 patients. Immunohistochemistry was performed to determine programmed death (PD)-1, CD8, and forkhead box P3 (FOXP3) expression by stromal tumor-infiltrating lymphocytes, and PD-ligand (L1) and PD-L2 expression by cancer cells. RESULTS: Of the 10 patients, 5 were responders (partial response) and 5 were non-responders (stable disease, 2; progressive disease, 3) to eribulin. PD-1, PD-L2, and FOXP3 expression became negative in 5 patients, PD-L1 expression became negative in 6 patients, and CD8 expression became positive in 3 patients after treatment. The response to eribulin was significantly associated with PD-L1 and FOXP3 negative conversion (p=0.024 and 0.004, respectively). The change in E-cadherin expression (positive or negative) was also correlated with the changes in PD-L1 and FOXP3 (p=0.024 and 0.004, respectively). Kaplan-Meier analysis with log-rank tests revealed that progression-free survival and time-to-treatment failure were significantly longer in patients with PD-L1 and FOXP3 negative conversion (p=0.012 and 0.001; p=0.049 and 0.018, respectively). CONCLUSION: The efficacy of eribulin may be attributed to its biological effects on the immune system (reduction of PD-L1 and FOXP3 expression) through epithelial-mesenchymal transition suppression, and vascular remodeling and improvement of the tumor microenvironment. Copyright
BACKGROUND/AIM: Several proteins involved in immune regulation and the relationship among these, the tumor microenvironment, and clinical outcomes of eribulin treatment were evaluated in advanced or metastatic breast cancerpatients. PATIENTS AND METHODS: This retrospective cohort study comprised 52 eribulin-treated locally advanced or metastatic breast cancerpatients. Cancer tissue samples were obtained before and after treatment in 10 patients. Immunohistochemistry was performed to determine programmed death (PD)-1, CD8, and forkhead box P3 (FOXP3) expression by stromal tumor-infiltrating lymphocytes, and PD-ligand (L1) and PD-L2 expression by cancer cells. RESULTS: Of the 10 patients, 5 were responders (partial response) and 5 were non-responders (stable disease, 2; progressive disease, 3) to eribulin. PD-1, PD-L2, and FOXP3 expression became negative in 5 patients, PD-L1 expression became negative in 6 patients, and CD8 expression became positive in 3 patients after treatment. The response to eribulin was significantly associated with PD-L1 and FOXP3 negative conversion (p=0.024 and 0.004, respectively). The change in E-cadherin expression (positive or negative) was also correlated with the changes in PD-L1 and FOXP3 (p=0.024 and 0.004, respectively). Kaplan-Meier analysis with log-rank tests revealed that progression-free survival and time-to-treatment failure were significantly longer in patients with PD-L1 and FOXP3 negative conversion (p=0.012 and 0.001; p=0.049 and 0.018, respectively). CONCLUSION: The efficacy of eribulin may be attributed to its biological effects on the immune system (reduction of PD-L1 and FOXP3 expression) through epithelial-mesenchymal transition suppression, and vascular remodeling and improvement of the tumor microenvironment. Copyright
Authors: Takaaki Oba; Mayu Ono; Hisanori Matoba; Takeshi Uehara; Yoshie Hasegawa; Ken-Ichi Ito Journal: Breast Cancer Res Treat Date: 2021-01-16 Impact factor: 4.872
Authors: Liubov A Tashireva; Nataliya O Popova; Anna Yu Kalinchuk; Viktor E Goldberg; Elena I Kovalenko; Elena V Artamonova; Aleksey G Manikhas; Dmitriy M Ponomarenko; Nataliya V Levchenko; Elena I Rossokha; Svetlana Yu Krasilnikova; Marina A Zafirova; Evgeniy L Choynzonov; Vladimir M Perelmuter Journal: Front Oncol Date: 2022-06-23 Impact factor: 5.738