Department of Medical Oncology, Shanghai Pulmonary Hospital,Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No 507 Zhengmin Road, Shanghai 200433, China.
Tongji University, No 1239 Siping Road, Shanghai 200433, China.
J Immunother Cancer. 2020 Oct;8(2). doi: 10.1136/jitc-2020-001391.
For small cell lung cancer (SCLC) therapy, immunotherapy might have unique advantages to some extent. Galectin-9 (Gal-9) plays an important role in antitumor immunity, while little is known of its function in SCLC.
By mean of immunohistochemistry (IHC), we tested the expression level of Gal-9 and other immune markers on both tumor cells and tumor-infiltrating lymphocytes (TILs) in 102 surgical-resected early stage SCLC clinical samples. On the basis of statistical analysis and machine learning results, the Gal-9-based immune risk score model was constructed and its predictive performance was evaluated. Then, we thoroughly explored the effects of Gal-9 and immune risk score on SCLC immune microenvironment and immune infiltration in different cohorts and platforms.
In the SCLC cohort for IHC, the expression level of Gal-9 on TILs was statistically correlated with the levels of program death-1 (p=0.001), program death-ligand 1 (PD-L1) (p<0.001), CD3 (p<0.001), CD4 (p<0.001), CD8 (p<0.001), and FOXP3 (p=0.047). High Gal-9 protein expression on TILs indicated better recurrence-free survival (30.4 months, 95% CI: 23.7-37.1 vs 39.4 months, 95% CI: 31.6-47.3, p=0.009). The immune risk score model which consisted of Gal-9 on TILs, CD4, and PD-L1 on TILs was established and validated so as to differentiate high-risk or low-risk patients with SCLC. The prognostic predictive performance of immune risk score model was better than single immune biomarker (area under the curve 0.671 vs 0.621-0.644). High Gal-9-related enrichment pathways in SCLC were enriched in immune system diseases and rheumatic disease. Furthermore, we found that patients with SCLC with low immune risk score presented higher fractions of activated memory CD4 T cells than patients with high immune risk score (p=0.048).
Gal-9 is markedly related to tumor-immune microenvironment and immune infiltration in SCLC. This study emphasized the predictive value and promising clinical applications of Gal-9 in stage I-III SCLC.
对于小细胞肺癌（SCLC）的治疗，免疫疗法可能在某种程度上具有独特的优势。半乳糖凝集素-9（Gal-9）在抗肿瘤免疫中发挥重要作用，但对其在 SCLC 中的作用知之甚少。
通过免疫组织化学（IHC），我们检测了 102 例手术切除的早期 SCLC 临床样本中肿瘤细胞和肿瘤浸润淋巴细胞（TIL）上 Gal-9 和其他免疫标志物的表达水平。基于统计分析和机器学习结果，构建了基于 Gal-9 的免疫风险评分模型，并评估了其预测性能。然后，我们在不同的队列和平台上深入探讨了 Gal-9 和免疫风险评分对 SCLC 免疫微环境和免疫浸润的影响。
在 SCLC 的 IHC 队列中，TILs 上 Gal-9 的表达水平与程序性死亡受体-1（p=0.001）、程序性死亡配体 1（PD-L1）（p<0.001）、CD3（p<0.001）、CD4（p<0.001）、CD8（p<0.001）和 FOXP3（p=0.047）的水平呈统计学相关。TILs 上高 Gal-9 蛋白表达预示着更好的无复发生存（30.4 个月，95%CI：23.7-37.1 与 39.4 个月，95%CI：31.6-47.3，p=0.009）。基于 TILs 上的 Gal-9、CD4 和 TILs 上的 PD-L1 建立和验证了免疫风险评分模型，以区分 SCLC 的高危或低危患者。免疫风险评分模型的预后预测性能优于单一免疫生物标志物（曲线下面积 0.671 与 0.621-0.644）。在 SCLC 中，与 Gal-9 相关的高富集途径富集在免疫系统疾病和风湿性疾病中。此外，我们发现低免疫风险评分的 SCLC 患者比高免疫风险评分的患者具有更高比例的激活记忆 CD4 T 细胞（p=0.048）。
Gal-9 在 SCLC 中与肿瘤免疫微环境和免疫浸润密切相关。本研究强调了 Gal-9 在 I-III 期 SCLC 中的预测价值和有前景的临床应用。
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