Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
School of Medicine, Tongji University, Shanghai, China.
Oncoimmunology. 2021 Jul 13;10(1):1947665. doi: 10.1080/2162402X.2021.1947665. eCollection 2021.
Pulmonary sarcomatoid carcinoma (PSC) is an uncommon subtype of lung cancer, and immune checkpoint blockade promises in clinical benefit. However, virtually nothing is known about the expression of common immune checkpoints in PSC. Here, we performed immunohistochemistry (IHC) to detect nine immune-related proteins in 97 PSC patients. Based on the univariable Cox regression, random forests were used to establish risk models for OS and DFS. Moreover, we used the GSEA, CIBERSORT, and ImmuCellAI to analyze the enriched pathways and microenvironment. Univariable analysis revealed that CD4 ( = 0.008), programmed cell death protein 1 (PD-1; = 0.003), galectin-9 (Gal-9) on tumor cells (TCs; = 0.021) were independent for DFS, while CD4 ( = 0.020), PD-1 ( = 0.004), Gal-9 ( = 0.033), and HLA on TILs ( = 0.031) were significant for OS. Meanwhile, the expression level of CD8 played a marginable role in DFS ( = 0.061), limited by the number of patients. The combination of Gal-9 on TC with CD4 and PD-1 on TILs demonstrated the most accurate prediction for DFS (AUC: 0.636-0.791, F1-score: 0.635-0.799), and a dramatic improvement to TNM-stage ( < 0.001 for F1-score of 1-y, 3-y, and 5-yDFS). A similar finding was also observed in the predictive ability of CD4 for OS (AUC: 0.602-0.678, F1-score: 0.635-0.679). CD4 was negatively associated with the infiltration of neutrophils ( = 0.015). PDCD1 (coding gene of PD-1) was positively correlated to the number of exhausted T cells (Texs; = 0.020) and induced regulatory T cells (iTregs; = 0.021), and LGALS9 (coding gene of Gal-9) was positively related to the level of dendritic cells (DCs; = 0.021). Further, a higher combinational level of CD4, PDCD1 on TILs, and LAGLS9 on TCs were proved to be infiltrated with more M1-type macrophages ( < 0.05). We confirmed the expression status of nine immune-related proteins and established a TNM-Immune system for OS and DFS in PSC to assist clinical risk-stratification.
肺肉瘤样癌（PSC）是一种罕见的肺癌亚型，免疫检查点阻断在临床上有获益的前景。然而，实际上对于 PSC 中常见免疫检查点的表达情况知之甚少。在这里，我们对 97 例 PSC 患者进行了免疫组化（IHC）检测，以检测 9 种与免疫相关的蛋白。基于单变量 Cox 回归，随机森林被用于建立 OS 和 DFS 的风险模型。此外，我们使用 GSEA、CIBERSORT 和 ImmuCellAI 来分析富集的通路和微环境。单变量分析显示，CD4（=0.008）、程序性死亡蛋白 1（PD-1；=0.003）、肿瘤细胞（TCs）上的半乳糖凝集素-9（Gal-9；=0.021）是 DFS 的独立预后因素，而 CD4（=0.020）、PD-1（=0.004）、Gal-9（=0.033）和 TILs 上的人类白细胞抗原（HLA；=0.031）是 OS 的显著预后因素。同时，CD8 的表达水平在 DFS 中也起着重要作用（=0.061），但受患者数量的限制。TCs 上的 Gal-9 与 TILs 上的 CD4 和 PD-1 的组合对 DFS 的预测最为准确（AUC：0.636-0.791，F1 得分：0.635-0.799），并极大地改善了 TNM 分期（1 年、3 年和 5 年 DFS 的 F1 得分<0.001）。在 CD4 对 OS 的预测能力中也观察到了类似的发现（AUC：0.602-0.678，F1 得分：0.635-0.679）。CD4 与中性粒细胞浸润呈负相关（=0.015）。PDCD1（PD-1 的编码基因）与耗竭性 T 细胞（Texs；=0.020）和诱导性调节性 T 细胞（iTregs；=0.021）的数量呈正相关，LGALS9（Gal-9 的编码基因）与树突状细胞（DCs；=0.021）的水平呈正相关。进一步研究发现，TILs 上的 CD4 和 PDCD1 以及 TCs 上的 LGALS9 联合水平较高的患者，其 M1 型巨噬细胞浸润更多（<0.05）。我们证实了 9 种免疫相关蛋白的表达状态，并建立了 PSC 用于 OS 和 DFS 的 TNM-免疫系统，以协助临床风险分层。
