引言
肿瘤相关巨噬细胞(tumor -associated macrophages, TAMs)是人类肿瘤中除癌细胞外主要表达程序性细胞死亡配体1 (programmed cell death ligand 1, PD-L1)的细胞，PD-L1
+
TAMs通常被认为在肿瘤免疫微环境中具有免疫抑制作用(TIME)。
2024年3月20日，深圳大学王雷及希望之城国家医学中心 Peter P. Lee共同通讯在
Cell Reports Medicine
在线发表题为“
PD-L1-expressing tumor-associated macrophages are immunostimulatory and associate with good clinical outcome in human breast cancer”的研究论文，该研究通过单细胞转录组学和空间多重免疫荧光分析，发现PD-L1
+ TAMs是成熟的，具有免疫刺激作用，对T细胞具有空间偏好。
相反，PD-L1
- TAMs具有免疫抑制作用，并与癌细胞在空间上共定位。在两个独立的乳腺癌患者队列中，较高的PD-L1
+ TAMs密度或PD-L1
+ /PDL1
- TAMs比例与良好的临床结果相关。在机制上，发现PD-L1在单核细胞向巨噬细胞的成熟和分化过程中上调，不需要外部IFN-γ刺激。功能上，PD-L1
+ TAMs更成熟/活化，促进CD8
+ T细胞增殖和细胞毒能力。总之，该研究揭示了PD-L1在时间内的免疫学意义。
程序性细胞死亡配体1 (Programmed cell death ligand 1, PD-L1)是PD-1的配体，它不仅可以在癌细胞中表达，也可以在肿瘤免疫微环境(TIME)内的骨髓细胞中表达。
已经证实，表达PD-L1的癌细胞可以通过直接抑制PD-L1
+ T细胞的细胞毒性而产生适应性免疫抵抗。最近的研究表明，肿瘤相关巨噬细胞(tumor-associated macrophages, TAMs)是人体内主要表达PD-L1的细胞。
PD-L1
+ TAMs在人肿瘤中的生物学意义和功能作用尚不清楚。
基于小鼠肿瘤模型的机制研究表明，表达PD-L1的TAMs在抑制抗肿瘤免疫中发挥重要作用。
然而，临床研究表明，在未经免疫治疗的肺癌、肝癌、乳腺癌(BC)患者中，表达PD-L1的TAMs与更好的总生存率相关。此外，在膀胱癌、尿路上皮癌或BC患者中，骨髓细胞表达PD-L1比癌细胞表达PD-L1更能预测PD-L1 /PD-L1阻断的反应。
这些关于表达PD-L1的TAMs的对比发现提出了PD-L1表达在TAMs上的免疫调节功能意义的重要问题。
通过单细胞RNA测序(scRNA-seq)对人类TAMs进行转录组学分析，发现其异质性较高，但缺乏PD-L1的表达。
这可能是由于PD-L1基因从scRNA-seq数据中缺失，因为它是一个低丰度的转录。利用scRNA-seq数据进行生物信息学模拟的研究报道，人类PD-L1
+TAMs上调抗原呈递基因，可能对T细胞具有免疫抑制作用。另一方面，通过离体功能测定的研究报道，
肺癌患者的PD-L1
+ TAMs可能不会抑制自体肿瘤特异性T细胞的癌细胞杀伤能力，反映了人类PD-L1
+ TAMs功能的不一致性。
模式图（Credit:
Cell Reports Medicine）
该研究揭示了PD-L1表达在人乳腺肿瘤TAMs中的功能和临床意义。
scRNA-seq数据、细胞-细胞空间相互作用分析和离体功能分析的集体发现表明，PD-L1
+ TAMs具有免疫刺激作用，而不是通常认为的免疫抑制作用。因此，它们的存在反映了免疫活性时间，并可能解释为什么它们预测抗pPD-1/PD-L1 (ICI)治疗的反应。
需要进一步研究抗PD-1/PD-L1免疫疗法对体内PD-L1
+ TAMs功能的影响。
https://doi.org/10.1016/j.xcrm.2024.101420
|探索君
排版|探索君
文章来源|“iNature”
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rgba(250, 157, 59, .6);--weui-TAG-BACKGROUND-ORANGE: rgba(250, 157, 59, .1);--weui-TAG-TEXT-GREEN: rgba(6, 174, 86, .6);--weui-TAG-BACKGROUND-GREEN: rgba(6, 174, 86, .1);--weui-TAG-TEXT-BLUE: rgba(16, 174, 255, .6);--weui-TAG-BACKGROUND-BLUE: rgba(16, 174, 255, .1);--weui-TAG-TEXT-BLACK: rgba(255, 255, 255, .5);--weui-TAG-BACKGROUND-BLACK: rgba(255, 255, 255, .05)}}@media screen and (min-width:1024px) and (prefers-color-scheme:dark){body:not(.pages_skin_pc) .wx-root:not([data-weui-theme=light]),body:not(.pages_skin_pc) body:not([data-weui-theme=light]){--appmsgExtra-BG: #121212}}@media(prefers-color-scheme:dark){body:not([data-weui-theme=light]).my_comment_empty_data{background-color:#111}}body,.wx-root{--weui-BG-6: rgba(0, 0, 0, .05);--weui-ACTIVE-MASK: rgba(0, 0, 0, .05)}body,.wx-root{--weui-REDORANGE: #ff6146;--weui-BG-0: #ededed;--weui-BG-1: #f7f7f7;--weui-BG-2: #fff;--weui-BG-3: #f7f7f7;--weui-BG-4: #4c4c4c;--weui-BG-5: #fff;--weui-FG-0: rgba(0, 0, 0, .9);--weui-FG-HALF: rgba(0, 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