Background: The immune environment of the cancer tissue not only influences the response to immunotherapy, but also the response to and outcomes after other anti-cancer therapies. Thus, the importance of regulating and improving the cancer immune microenvironment is increasingly being recognized. Tumor-infiltrating lymphocytes (TILs) can be used to monitor the immune response and are important in predicting treatment responses and outcomes in various types of carcinoma. On the other hand, it was reported that eribulin suppresses epithelial-mesenchymal transition (EMT) in basic studies, and we investigated it with clinical
samples. In addition, it is thought that antitumor autoimmune response relates to suppression of EMT. In the present study, we investigated clinically antitumor autoimmune response in breast cancer with eribulin chemotherapy.
Materials and Methods: Eribulin chemotherapy was administered to 52 patients with locally advanced or metastatic breast cancer. Samples of cancer tissue obtained before and after treatment were available from 10 patients. We evaluated response rate (RR) and analyzed protein expression by immunostaining of specimens before and after treatment. We evaluated antitumor autoimmune response by PD-1, CD8, FOXP3 expression in stromal TILs and PD-L1, PD-L2 expression in cancer cells. And, we examined the relation between the expression of these immune related molecules and EMT markers (evaluated by E-cadherin, N-cadherin, Vimentin
Results: In 11 patients (21.2%), it was possible to excise the lesion after treatment. In 10 evaluable cases without one pathological complete response (pCR) case, PD-1, PD-L2, and FOXP3 expression turned to negative in 5 cases, PD-L1 expression turned to negative in 6 cases, and CD8 expression turned to positive in 3 cases before and after treatment with eribulin chemotherapy. Looking at the relation between the transition in this protein expression and therapeutic effect, cases observed with negative conversion in PD-L1, FOXP3 expression had significantly high RR (p = 0.024) (p = 0.004). Among high RR cases, CD-8 expression was increased, the PD-1, PD-L1 and FOXP3 expression were remarkably reduced. Furthermore, we found a inverse correlation between PD-L1, FOXP3 expression turning to negative and E-cadherin expression turning to positive (p = 0.024) (p = 0.004).
Conclusions: In the chemotherapy with eribulin, PD-L1 and FOXP3 expression turning to negative before and after treatment suggested improvement of the tumor immune microenvironment, and this mechanism related to suppression of EMT.
Citation Format: Wataru Goto, Shinichiro Kashiwagi, Yuka Asano, Kento Kurata, Tamami Morisaki, Satoru Noda, Tsutomu Takashima, Naoyoshi Onoda, Sayaka Tanaka, Masahiko Ohsawa, Masaichi Ohira, Kosei Hirakawa. Clinical verification of antitumor autoimmune response in eribulin chemotherapy for breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5127.