Characteristics of the immune microenvironment and their clinical significance in non-small cell lung cancer patients with ALK-rearranged mutation

作者：Bo Zhang, J. Zeng, H. Zhang, Shuai Zhu, Han-Jin Wang, Jinling He, Lingqi Yang, N. Zhou, L. Zu, Xiaohong Xu, Zuoqing Song, Song Xu · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.974581 · 被引用次数：25 · 研究领域：Medicine

Background Although immune checkpoint inhibitors (ICIs) are one of the most important treatments for advanced-stage non-small-cell lung cancer (NSCLC), NSCLC patients with ALK-rearranged usually don’t obtain a clinical benefit. The reason may be related to the unique tumor microenvironment (TME). We evaluated the characteristics of immune biomarkers of the TME and their prognostic value in ALK-rearranged NSCLC. Methods Tumor samples from patients with ALK-rearranged (N = 39) and EGFR- (N = 40)/KRAS- (N = 30) mutated NSCLC were collected. Immunohistochemistry (IHC) was used to assess the expression of 9 tumor immune markers as well as 6 immune markers of tumor-infiltrating cells. To research the TME of ALK-rearranged NSCLC, EGFR/KRAS-positive patients were used as controls. Furthermore, the correlation between the efficacy and prognosis of patients with advanced-stage (IIIC-IV) ALK rearrangements treated with targeted drugs was analyzed in terms of the TME. Results The proportion of PD-L1+ tumors was lower in ALK-positive NSCLC than in KRAS-positive NSCLC. Besides, the proportion of T cells expressing TIM-3-CD8+ (15.38%), CTLA4-CD8+ (12.82%), LAG3-CD8+ (33.33%) and PD-1-CD8+ (2.56%) in ALK-positive NSCLC was lower than that in EGFR/KRAS-positive NSCLC. The expression of CD3, CD8 T cells and CD20 B cells was lower in ALK-positive NSCLC than in KRAS-positive NSCLC (p < 0.0001, < 0.005, and < 0.001, respectively). Nevertheless, the level of CD4 helper T cells was higher in ALK-po...