Vankerckhoven Ann, Baert Thaïs, Riva Matteo, De Bruyn Christine, Thirion Gitte, Vandenbrande Katja, Ceusters Jolien, Vergote Ignace, Coosemans An
Department of Oncology, Leuven Cancer Institute, Laboratory of Tumor Immunology and Immunotherapy, KU Leuven, Leuven, Belgium.
Department of Oncology, Leuven Cancer Institute, Laboratory of Tumor Immunology and Immunotherapy, KU Leuven, Leuven, Belgium; Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte (KEM), Essen, Germany.
Transl Oncol. 2021 Jun;14(6):101076. doi: 10.1016/j.tranon.2021.101076. Epub 2021 Mar 23.
Chemotherapy induces a variety of immunological changes. Studying these effects can reveal opportunities for successful combining chemotherapy and immunotherapy. Immuno-chemotherapeutic combinations in ovarian cancer are currently not generating the anticipated positive effects. To date, only scattered and inconsistent information is available about the immune-induced changes by chemotherapy in ovarian cancer. In this study, we compared six common chemotherapeutics used in ovarian cancer patients (carboplatin, paclitaxel, pegylated liposomal doxorubicin, gemcitabine, carboplatin-paclitaxel and carboplatin-gemcitabine) and studied their effects on the immune system in an ovarian cancer mouse model. Mice received a single chemotherapy or vehicle injection 21 days after tumor inoculation with ID8-fluc cells. One week after therapy administration, we collected peritoneal washings for flow cytometry, serum for cytokine analysis with cytometric bead array and tumor biopsies for immunohistochemistry. Carboplatin-paclitaxel showed the most favorable profile with a decrease in immunosuppressive cells in the peritoneal cavity and an increase of interferon-gamma in serum. In contrast, carboplatin-gemcitabine seemed to promote a hostile immune environment with an increase in regulatory T-cells in tumor tissue and an increase of macrophage-inflammatory-protein-1-beta in the serum.
化疗会引发多种免疫变化。对这些效应进行研究能够揭示成功联合化疗与免疫疗法的机会。目前，卵巢癌的免疫化疗联合方案并未产生预期的积极效果。迄今为止，关于化疗在卵巢癌中引发的免疫变化，仅有零散且不一致的信息。在本研究中，我们比较了卵巢癌患者常用的六种化疗药物（卡铂、紫杉醇、聚乙二醇脂质体阿霉素、吉西他滨、卡铂 - 紫杉醇以及卡铂 - 吉西他滨），并在卵巢癌小鼠模型中研究了它们对免疫系统的影响。在用ID8 - fluc细胞接种肿瘤21天后，小鼠接受单次化疗或注射赋形剂。给药一周后，我们收集腹腔灌洗液用于流式细胞术检测，收集血清用于细胞因子微球阵列分析，收集肿瘤活检组织用于免疫组织化学检测。卡铂 - 紫杉醇表现出最有利的情况，腹腔内免疫抑制细胞减少，血清中γ - 干扰素增加。相比之下，卡铂 - 吉西他滨似乎促进了不利的免疫环境，肿瘤组织中调节性T细胞增加，血清中巨噬细胞炎性蛋白 - 1β增加。
