Giatromanolaki Alexandra, Mitrakas Achilleas, Anestopoulos Ioannis, Kontosis Andreas, Koukourakis Ioannis M, Pappa Aglaia, Panayiotidis Mihalis I, Koukourakis Michael I
Department of Pathology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
Department of Cancer Genetics, Therapeutics & Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus.
Cancers (Basel). 2022 Apr 1;14(7):1801. doi: 10.3390/cancers14071801.
Cancer cells escape macrophage phagocytosis by expressing the CD47 integrin-associated protein that binds to the SIRPα ligand (signal regulatory protein alpha) expressed by macrophages. Immunotherapy targeting this pathway is under clinical development.
We investigated the expression of CD47/SIRPα molecules in a series of 98 NSCLCs, in parallel with the infiltration of tumor stroma by CD68+ macrophages, tumor-infiltrating lymphocytes (TILs), and PD-L1/PD-1 molecules.
Extensive membranous CD47 expression by cancer cells characterized 29/98 cases. SIRPα and CD68 were expressed, to a varying extent, by tumor-associated macrophages (Μφ, TAMs). A high CD68Mφ-score in inner tumor areas was linked with improved overall survival ( = 0.005); and this was independent of the stage ( = 0.02, hazard ratio 0.4). In contrast, high SIRPα expression by CD68+ TAMs (SIRPα/CD68-ratio) was linked with CD47 expression by cancer cells, low TIL-score, and poor prognosis ( = 0.02). A direct association of CD47 expression by cancer cells and the % FOXP3+ TILs ( = 0.01, r = 0.25) was also noted.
TAMs play an important role in the prognosis of operable NSCLC. As SIRPα+ macrophages adversely affect prognosis, it is suggested that the CD47/SIRPα axis is a sound target for adjuvant immunotherapy policies, aiming to improve the cure rates in operable NSCLC.
癌细胞通过表达与巨噬细胞表达的信号调节蛋白α（SIRPα）配体结合的CD47整合素相关蛋白来逃避巨噬细胞的吞噬作用。针对该途径的免疫疗法正在进行临床开发。
我们研究了98例非小细胞肺癌（NSCLC）中CD47/SIRPα分子的表达情况，并同时观察了肿瘤基质中CD68 +巨噬细胞、肿瘤浸润淋巴细胞（TIL）和PD-L1/PD-1分子的浸润情况。
98例病例中有29例癌细胞呈现广泛的膜性CD47表达。肿瘤相关巨噬细胞（Μφ，TAMs）不同程度地表达SIRPα和CD68。肿瘤内部区域的高CD68Μφ评分与总生存期改善相关（P = 0.005）；且这与分期无关（P = 0.02，风险比0.4）。相反，CD68 + TAMs的高SIRPα表达（SIRPα/CD68比值）与癌细胞的CD47表达、低TIL评分及预后不良相关（P = 0.02）。还注意到癌细胞的CD47表达与FOXP3 + TIL的百分比直接相关（P = 0.01，r = 0.25）。
TAMs在可手术NSCLC的预后中起重要作用。由于SIRPα +巨噬细胞对预后产生不利影响，提示CD47/SIRPα轴是辅助免疫治疗策略的合理靶点，旨在提高可手术NSCLC的治愈率。
