School of Clinical Medicine, Shandong Second Medical University, Weifang, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Cancer Sci. 2024 Aug;115(8):2528-2539. doi: 10.1111/cas.16206. Epub 2024 May 8.
Occult lymph node metastasis (OLNM) is one of the main causes of regional recurrence in inoperable N non-small cell lung cancer (NSCLC) patients following stereotactic ablation body radiotherapy (SABR) treatment. The integration of immunotherapy and SABR (I-SABR) has shown preliminary efficiency in mitigating this recurrence. Therefore, it is necessary to explore the functional dynamics of critical immune effectors, particularly CD8 T cells in the development of OLNM. In this study, tissue microarrays (TMAs) and multiplex immunofluorescence (mIF) were used to identify CD8 T cells and functional subsets (cytotoxic CD8 T cells/predysfunctional CD8 T cells (CD8 T)/dysfunctional CD8 T cells (CD8 T)/other CD8 T cells) among the no lymph node metastasis, OLNM, and clinically evident lymph node metastasis (CLNM) groups. As the degree of lymph node metastasis escalated, the density of total CD8 T cells and CD8 T cells, as well as their proximity to tumor cells, increased progressively and remarkably in the invasive margin (IM). In the tumor center (TC), both the density and proximity of CD8 T cells to tumor cells notably decreased in the OLNM group compared with the group without metastasis. Furthermore, positive correlations were found between the dysfunction of CD8 T cells and HIF-1αCD8 and cancer microvessels (CMVs). In conclusion, the deterioration in CD8 T cell function and interactive dynamics between CD8 T cells and tumor cells play a vital role in the development of OLNM in NSCLC. Strategies aimed at improving hypoxia or targeting CMVs could potentially enhance the efficacy of I-SABR.
隐匿性淋巴结转移（OLNM）是立体定向消融体放射治疗（SABR）治疗后不可手术的 N 期非小细胞肺癌（NSCLC）患者区域性复发的主要原因之一。免疫治疗与 SABR 的联合（I-SABR）已初步显示出减轻这种复发的效果。因此，有必要探索关键免疫效应器（特别是 CD8 T 细胞）在 OLNM 发展过程中的功能动态。在这项研究中，组织微阵列（TMA）和多重免疫荧光（mIF）用于识别无淋巴结转移、OLNM 和临床明显淋巴结转移（CLNM）组中的 CD8 T 细胞和功能亚群（细胞毒性 CD8 T 细胞/功能前 CD8 T 细胞（CD8 T）/功能障碍 CD8 T 细胞（CD8 T）/其他 CD8 T 细胞）。随着淋巴结转移程度的增加，总 CD8 T 细胞和 CD8 T 细胞的密度及其在侵袭边缘（IM）中与肿瘤细胞的接近程度逐渐显著增加。在肿瘤中心（TC）中，与无转移组相比，OLNM 组 CD8 T 细胞与肿瘤细胞的密度及其接近程度显著降低。此外，还发现 CD8 T 细胞的功能障碍与 HIF-1αCD8 和癌微血管（CMVs）之间存在正相关。总之，CD8 T 细胞功能的恶化以及 CD8 T 细胞与肿瘤细胞之间的相互作用动态在 NSCLC 中 OLNM 的发展中起着至关重要的作用。旨在改善缺氧或靶向 CMVs 的策略可能会增强 I-SABR 的疗效。
