中文摘要：
單核吞噬細胞（MPs）在維持組織穩態中發揮關鍵作用，但同時也會促進腫瘤進展，并導致腫瘤對免疫檢查點阻斷療法（ICB）產生耐藥。靶向單核吞噬細胞有望成為提升免疫檢查點阻斷療效的有效策略。本研究證實，絲氨酸 / 蘇氨酸激酶蛋白激酶 Cδ（PKCδ） 在人和小鼠腫瘤內的單核吞噬細胞中呈高表達。
與野生型小鼠相比，PKCδ 基因敲除（PKCδ?/?） 小鼠的腫瘤進展受到抑制，且對抗 PD-1 療法的應答提升。PKCδ?/?小鼠的腫瘤微環境呈現偏向 Th1 型的免疫應答特征，抗原提呈能力與 T 細胞活化水平均有所增強。
在活體動物中清除單核吞噬細胞后，野生型小鼠的腫瘤生長受到影響，而 PKCδ?/?小鼠則無明顯變化。將 PKCδ?/?的 M2 樣巨噬細胞與腫瘤細胞共同接種至野生型小鼠體內，相較于野生型（PKCδ?/?）對照組，可顯著延緩腫瘤生長，并大幅增強腫瘤內部的 T 細胞活化。
PKCδ 基因缺失可通過激活I 型與 II 型干擾素信號通路，實現單核吞噬細胞的表型重編程。綜上，靶向 PKCδ 能夠重塑單核吞噬細胞功能，進而增強免疫檢查點阻斷療法的抗腫瘤效果。
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.
論文信息：
論文題目：Protein kinase C delta regulates mononuclear phagocytes and hinders response to immunotherapy in cancer
期刊名稱：Science Advances
時間期卷：Vol 7, Issue 51(2023)
在線時間：2023年12月22日
DOI: 10.1126/sciadv.add3231
產品信息：
貨號：CP-005-005
規格：5ml+5ml
品牌：Liposoma
產地：荷蘭
名稱：Clodronate Liposomes&Control Liposomes
辦事處：靶點科技
Clodronate Liposomes氯膦酸鹽脂質體在敲除小鼠腫瘤模型種清除巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Science Advances：蛋白激酶 Cδ 調控單核吞噬細胞，并削弱腫瘤的免疫治療應答。
Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除巨噬細胞的材料和方法：
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].
巨噬細胞清除材料和方法文獻截圖：
