Abstract：
Tumor-associated macrophages (TAMs) accumulate in the solid tumor microenvironment (TME) and have been shown to promote tumor growth and dampen antitumor immune responses. TAM-mediated suppression of T-cell antitumor reactivity is considered to be a major obstacle for many immunotherapies, including immune checkpoint blockade and adoptive T/CAR-T-cell therapies. An ex vivo culture system closely mimicking the TME can greatly facilitate the study of cancer immunotherapies. Here, we report the development of a 3D TME-mimicry culture that is comprised of the three major components of a human TME, including human tumor cells, TAMs, and tumor antigen-specific T cells. This TME-mimicry culture can readout the TAM-mediated suppression of T-cell antitumor reactivity, and therefore can be used to study TAM modulation of T-cell-based cancer immunotherapy. As a proof-of-principle, the studies of a PD-1/PD-L1 blockade therapy and a MAO-A blockade therapy were performed and validated.
摘要：
肿瘤相关巨噬细胞（TAM）在实体瘤微环境（TME）中积累，并已被证明可促进肿瘤生长并抑制抗肿瘤免疫反应。TAM介导的T细胞抗肿瘤反应性抑制被认为是许多免疫疗法的主要障碍。包括免疫检查点阻断和过继性T/CAR-T细胞疗法。紧密模拟TME的离体培养系统可以极大地促进癌症免疫疗法的研究。这里,我们报告了3DTME模拟文化的发展，该文化由人类TME的三个主要组成部分组成，包括人类肿瘤细胞，TAM,和肿瘤抗原特异性T细胞。这种TME模拟培养物可以读出TAM介导的T细胞抗肿瘤反应性抑制，因此可用于研究基于T细胞的癌症免疫疗法的TAM调节。作为一个原则证明,我们进行了PD-1/PD-L1阻断治疗和MAO-A阻断治疗的研究,并进行了验证.
