中文摘要：
单核吞噬细胞（MPs）在维持组织稳态中发挥关键作用，但同时也会促进肿瘤进展，并导致肿瘤对免疫检查点阻断疗法（ICB）产生耐药。靶向单核吞噬细胞有望成为提升免疫检查点阻断疗效的有效策略。本研究证实，丝氨酸 / 苏氨酸激酶蛋白激酶 Cδ（PKCδ） 在人和小鼠肿瘤内的单核吞噬细胞中呈高表达。
与野生型小鼠相比，PKCδ 基因敲除（PKCδ?/?） 小鼠的肿瘤进展受到抑制，且对抗 PD-1 疗法的应答提升。PKCδ?/?小鼠的肿瘤微环境呈现偏向 Th1 型的免疫应答特征，抗原提呈能力与 T 细胞活化水平均有所增强。
在活体动物中清除单核吞噬细胞后，野生型小鼠的肿瘤生长受到影响，而 PKCδ?/?小鼠则无明显变化。将 PKCδ?/?的 M2 样巨噬细胞与肿瘤细胞共同接种至野生型小鼠体内，相较于野生型（PKCδ?/?）对照组，可显著延缓肿瘤生长，并大幅增强肿瘤内部的 T 细胞活化。
PKCδ 基因缺失可通过激活I 型与 II 型干扰素信号通路，实现单核吞噬细胞的表型重编程。综上，靶向 PKCδ 能够重塑单核吞噬细胞功能，进而增强免疫检查点阻断疗法的抗肿瘤效果。
英文摘要：
Mononuclear phagocytes (MPs) play a crucial role in tissue homeostasis; however, MPs also contribute to tumor progression and resistance to immune checkpoint blockade (ICB). Targeting MPs could be an effective strategy to enhance ICB efficacy. We report that protein kinase C delta (PKCδ), a serine/threonine kinase, is abundantly expressed by MPs in human and mouse tumors. PKCδ?/? mice displayed reduced tumor progression compared to wild types, with increased response to anti–PD-1. Tumors from PKCδ?/? mice demonstrated TH1-skewed immune response including increased antigen presentation and T cell activation. Depletion of MPs in vivo altered tumor growth in control but not PKCδ?/? mice. Coinjection of PKCδ?/? M2-like macrophages with cancer cells into wild-type mice markedly delayed tumor growth and significantly increased intratumoral T cell activation compared to PKCδ+/+ controls. PKCδ deficiency reprogrammed MPs by activating type I and type II interferon signaling. Thus, PKCδ might be targeted to reprogram MPs to augment ICB efficacy.
论文信息：
论文题目：Protein kinase C delta regulates mononuclear phagocytes and hinders response to immunotherapy in cancer
期刊名称：Science Advances
时间期卷：Vol 7, Issue 51(2023)
在线时间：2023年12月22日
DOI: 10.1126/sciadv.add3231
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体在敲除小鼠肿瘤模型种清除巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Science Advances：蛋白激酶 Cδ 调控单核吞噬细胞，并削弱肿瘤的免疫治疗应答。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
All reagents were obtained from Sigma-Aldrich (St. Louis, MO) unless otherwise noted. Fetal bovine serum (FBS; Gibco, Waltham, MA), 100× l-glutamine, 100× penicillin/streptomycin HyClone (Pittsburgh, PA), and Gibco 100× antibiotic mix were obtained from Thermo Fisher Scientific (Waltham, MA). RPMI 1640, Dulbecco’s modified Eagle’s medium (DMEM), and Matrigel are from Corning (Tewksbury, MA). Mouse recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin- 6 (IL-6), IL-4, macrophage CSF (M-CSF), and FMS-like tyrosine kinase 3 ligand (FLT3L) were obtained from BioLegend (San Diego, CA). OVA was obtained from Thermo Fisher Scientific. Mouse IFN-γ ELISA kit was obtained from R&D Systems (Minneapolis, MN). Mouse CD4+ T cell isolation kit and CD8+ T cell isolation kit were obtained from Miltenyi Biotec (Auburn, CA). Clodronate and control liposomes were obtained from Liposoma (Amsterdam, The Netherlands). In vivo anti-mouse CD40, anti-mouse PD-1, anti-mouse Ly6C monoclonal antibodies, and their controls (rat IgG2a) were all obtained from Bio X Cell (Lebanon, NH). KO-validated PKCδ antibody and phycoerythrin/Cy7 conjugation kit were obtained from Abcam (Cambridge, UK). Flow cytometry antibodies, compensation beads, and reagents are described in table S1 [Tonbo Biosciences Inc. (San Diego, CA), Thermo Fisher, and BioLegend].
巨噬细胞清除材料和方法文献截图：
