美国冷泉港实验室Mikala Egeblad团队发现，激活协同先天适应性免疫反应能够控制转移。2021年9月2日，《癌细胞》杂志在线发表了这项成果。

研究人员表明，乳腺癌患者转移性胸腔积液中的巨噬细胞可以通过单磷酸脂A（MPLA）和干扰素（IFN）γ进行极化以杀死癌细胞。MPLA+IFNγ在肿瘤内或腹腔内注射可以减少乳腺癌小鼠模型的原发肿瘤生长和转移，抑制转移，并增强卵巢癌模型的化疗反应。巨噬细胞和T细胞对该疗法的抗转移作用都很关键。

MPLA+IFNγ刺激I型IFN信号，将CD206⁺ 肿瘤相关巨噬细胞（TAM）重新编程为诱导性NO合成酶（iNOS）⁺巨噬细胞，并通过巨噬细胞分泌的白细胞介素-2（IL-12）和肿瘤坏死因子α（TNFα）激活细胞毒性T细胞。MPLA和IFNγ在临床实践中被单独使用，它们一起可作为一种以前未曾探索过的参与全身性抗肿瘤免疫反应的方法。

据介绍，TAM促进转移并抑制T细胞，但巨噬细胞可以被极化以杀死癌细胞。因此，巨噬细胞极化可能是一种控制癌症的策略。

附：英文原文

Title: Activating a collaborative innate-adaptive immune response to control metastasis

Author: Lijuan Sun, Tim Kees, Ana Santos Almeida, Bodu Liu, Xue-Yan He, David Ng, Xiao Han, David L. Spector, Iain A. McNeish, Phyllis Gimotty, Sylvia Adams, Mikala Egeblad

Issue&Volume: 2021-09-02

Abstract: Tumor-associated macrophages (TAMs) promote metastasis and inhibit T cells, but macrophagescan be polarized to kill cancer cells. Macrophage polarization could thus be a strategyfor controlling cancer. We show that macrophages from metastatic pleural effusionsof breast cancer patients can be polarized to kill cancer cells with monophosphoryllipid A (MPLA) and interferon (IFN) γ. MPLA + IFNγ injected intratumorally or intraperitoneallyreduces primary tumor growth and metastasis in breast cancer mouse models, suppressesmetastasis, and enhances chemotherapy response in an ovarian cancer model. Both macrophagesand T cells are critical for the treatment's anti-metastatic effects. MPLA + IFNγstimulates type I IFN signaling, reprograms CD206+ TAMs to inducible NO synthase (iNOS)+ macrophages, and activates cytotoxic T cells through macrophage-secreted interleukin-2(IL-12) and tumor necrosis factor alpha (TNFα). MPLA and IFNγ are used individuallyin clinical practice and together represent a previously unexplored approach for engaginga systemic anti-tumor immune response.

DOI: 10.1016/j.ccell.2021.08.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00445-1