MDPIActa Medica Okayama1422-006723192022Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model11035ENTsukasaShigehiroResearch Institute for Biomedical Sciences, Tokyo University of ScienceMahoUenoDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversityMayumiKijihiraDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversityRyotaroTakahashiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityChihoUmemuraDivision of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityEman A.TahaDivision of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityChisakiKurosakaDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversityMegumiAsayamaDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversityHiroshiMurakamiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityJunichiroFutamiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJunkoMasudaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySecondary 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.MDPIActa Medica Okayama1422-00672052019Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel1042ENApriliana Cahya Khayrani Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityHafizahMahmud Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityMaram H.Zahra Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityAung Ko Ko Oo Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityMiharuOze Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityJuanDu Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityMd JahangirAlam Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversitySaid M.Afify Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityHagar A. Abu QuoraLaboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTsukasaShigehiro Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityAnna Sanchez Calle Division of Molecular and Cellular Medicine, National Cancer Center Research InstituteNobuhiroOkada Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAkimasaSenoLaboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKokiFujitaEnsuiko Sugar Refining Co., Ltd.HirokiHamadaFaculty of Science, Okayama University of ScienceYuhkiSeno Graduate School of Pharmaceutical Science, Tokushima UniversityTadakatsuMandai Faculty of Life Science, Kurashiki University of Science and the ArtsMasaharuSeno Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityPaclitaxel (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.