MDPI Acta Medica Okayama 1422-0067 23 19 2022 Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model 11035 EN Tsukasa Shigehiro Research Institute for Biomedical Sciences, Tokyo University of Science Maho Ueno Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Mayumi Kijihira Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Ryotaro Takahashi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Chiho Umemura Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Eman A. Taha Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Chisaki Kurosaka Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Megumi Asayama Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Hiroshi Murakami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Junichiro Futami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Junko Masuda Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-gamma production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-gamma expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103(+)CD11b(+) dendritic cells (DCs) into the mLN, along with increased (1 -> 3)-beta-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103(+)CD11b(+) DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 20 5 2019 Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel 1042 EN Apriliana Cahya Khayrani Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Hafizah Mahmud Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Maram H. Zahra Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Aung Ko Ko Oo Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Miharu Oze Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Juan Du Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Md Jahangir Alam Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Said M. Afify Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Hagar A. Abu Quora Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tsukasa Shigehiro Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Anna Sanchez Calle Division of Molecular and Cellular Medicine, National Cancer Center Research Institute Nobuhiro Okada Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akimasa Seno Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Koki Fujita Ensuiko Sugar Refining Co., Ltd. Hiroki Hamada Faculty of Science, Okayama University of Science Yuhki Seno Graduate School of Pharmaceutical Science, Tokushima University Tadakatsu Mandai Faculty of Life Science, Kurashiki University of Science and the Arts Masaharu Seno Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Paclitaxel (PTX) is one of the front-line drugs approved for the treatment of ovarian cancer. However, the application of PTX is limited due to the significant hydrophobicity and poor pharmacokinetics. We previously reported target-directed liposomes carrying tumor-selective conjugated antibody and encapsulated glycosylated PTX (gPTX-L) which successfully overcome the PTX limitation. The tubulin stabilizing activity of gPTX was equivalent to that of PTX while the cytotoxic activity of gPTX was reduced. In human ovarian cancer cell lines, SK-OV-3 and OVK18, the concentration at which cell growth was inhibited by 50% (IC50) for gPTX range from 15⁻20 nM, which was sensitive enough to address gPTX-L with tumor-selective antibody coupling for ovarian cancer therapy. The cell membrane receptor CD44 is associated with cancer progression and has been recognized as a cancer stem cell marker including ovarian cancer, becoming a suitable candidate to be targeted by gPTX-L therapy. In this study, gPTX-loading liposomes conjugated with anti-CD44 antibody (gPTX-IL) were assessed for the efficacy of targeting CD44-positive ovarian cancer cells. We successfully encapsulated gPTX into liposomes with the loading efficiency (LE) more than 80% in both of gPTX-L and gPTX-IL with a diameter of approximately 100 nm with efficacy of enhanced cytotoxicity in vitro and of convenient treatment in vivo. As the result, gPTX-IL efficiently suppressed tumor growth in vivo. Therefore gPTX-IL could be a promising formulation for effective ovarian cancer therapies. No potential conflict of interest relevant to this article was reported.