肿瘤相关巨噬细胞衍生的可溶性PD-L1在非小细胞肺癌的预后影响。
Prognostic impact of soluble PD-L1 derived from tumor-associated macrophages in non-small-cell lung cancer.
发表日期:2023 Aug 30
作者:
Koji Teramoto, Tomoyuki Igarashi, Yoko Kataoka, Mitsuaki Ishida, Jun Hanaoka, Hidetoshi Sumimoto, Yataro Daigo
来源:
Cell Death & Disease
摘要:
肿瘤细胞上的程序性细胞死亡配体-1(PD-L1)可以被降解为可溶性形式(sPD-L1)并进入血液循环,然而,sPD-L1在周边血液中的临床意义在非小细胞肺癌(NSCLC)中尚待阐明。我们在手术期间监测了患有可手术治疗的NSCLC患者的血浆sPD-L1水平,并评估了肿瘤组织中的PD-L1阳性细胞。然后,回顾性分析了术前血浆sPD-L1水平与无复发存活期(RFS)之间的相关性。在接受根治手术的患者中(n=61),手术后1个月血浆sPD-L1水平(中位数;63.5 pg/mL)显著增加(72.2 pg/mL,P<0.001)。包括肿瘤细胞和肿瘤相关巨噬细胞(TAMs)的PD-L1阳性细胞的综合评分与术前血浆sPD-L1水平显著相关。在术前血浆sPD-L1水平较高的患者中,相对于术前tcPD-L1表达强度高的患者,术前tcPD-L1表达强度低的患者的5年RFS概率显著差(分别为33.3%和87.5%,P=0.016;95% CI, 0.013-0.964)。在前者组中,PD-L1阳性TAMs的浸润明显高于后者组(分别为246.4和76.6个计数/ mm2,P =0.003)。在NSCLC中,血浆sPD-L1可以反映PD-L1阳性TAMs的积累,而不仅仅是PD-L1阳性肿瘤细胞。在术前血浆sPD-L1水平较高的患者中,术后预后取决于PD-L1阳性细胞(肿瘤细胞或TAMs)是sPD-L1的主要来源。因此,同时测量血浆sPD-L1水平和肿瘤细胞和TAMs的PD-L1表达情况有助于评估可手术NSCLC的术后预后。© 2023. The Author(s).
Programmed cell death-ligand 1 (PD-L1) on tumor cells can be degraded to soluble form (sPD-L1) and enter circulation, however, the clinical significances of sPD-L1 in peripheral blood remains to be elucidated in non-small-cell lung cancer (NSCLC). We monitored plasma sPD-L1 levels during perioperative periods and evaluated PD-L1-positive cells in tumor tissues in patients with operable NSCLC. Then the correlation between preoperative plasma sPD-L1 levels and relapse-free survival (RFS) was analyzed retrospectively. In patients who underwent radical surgery (n = 61), plasma sPD-L1 levels (median; 63.5 pg/mL) significantly increased 1 month after surgery (72.2 pg/mL, P < 0.001). The combined score of PD-L1-positive cells including tumor cells and tumor-associated macrophages (TAMs) was significantly associated with preoperative plasma sPD-L1 levels. In patients with high levels of preoperative plasma sPD-L1, the probability of 5-year RFS was significantly poor for patients with low PD-L1 expression intensity of tumor cells (tcPD-L1) compared with those with high tcPD-L1 (33.3% vs. 87.5%, respectively, P = 0.016; 95% CI, 0.013-0.964). In former group, PD-L1-positive TAMs were markedly infiltrating compared with those from latter group (246.4 vs. 76.6 counts/mm2, respectively, P = 0.003). In NSCLC, plasma sPD-L1 can reflect the accumulation of PD-L1-posotive TAMs, not just PD-L1-positive tumor cells. In patients with high levels of preoperative plasma sPD-L1, the prognoses after surgery depends on which PD-L1-positive cells, tumor cells or TAMs, are the primary source of the sPD-L1. Thus, measuring both plasma sPD-L1 levels and PD-L1 expression status of tumor cells and TAMs is of benefit for assessment of postoperative prognosis in operable NSCLC.© 2023. The Author(s).