Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Oncoimmunology. 2022 Nov 23;11(1):2148374. doi: 10.1080/2162402X.2022.2148374. eCollection 2022.
A better understanding of the effects of preoperative chemoradiotherapy (CRT) on tumor immune microenvironment (TIME) is essential to improve the treatment outcomes of patients with locally advanced rectal cancer (LARC). In this context, we performed a multiplex immunofluorescence staining to evaluate the TIME in 158 patients with LARC who underwent preoperative CRT followed by surgery and adjuvant chemotherapy in the ADORE trial. We found that higher levels of T-cell subsets (CD3, CD4, and CD8) and dendritic cells in the tumor compartment of pretreatment biopsy samples were associated with good response to preoperative CRT. After CRT, there was a significant increase in the densities of CD3 T cells, CD8 T cells, and dendritic cells, while that of CD4FoxP3 regulatory T cells decreased, indicating that CRT changed the TIME into a more immune-active status. However, CRT also conferred an immunosuppressive effect by polarizing the tumor-associated macrophages from pro-inflammatory M1 macrophage to immune-suppressive M2 macrophages and decreasing the density of B cells. High delta values of CD3 T cells and PD-L1 lymphocytes after CRT were associated with good disease-free survival (DFS), while that of CD4FoxP3 regulatory T cells was associated with poor DFS. These findings provide a framework for future studies incorporating strategies to modulate the TIME in patients with LARC.
更好地了解术前放化疗 (CRT) 对肿瘤免疫微环境 (TIME) 的影响，对于改善局部晚期直肠癌 (LARC) 患者的治疗效果至关重要。在这方面，我们进行了多重免疫荧光染色，以评估 ADORE 试验中 158 例接受术前 CRT 后手术和辅助化疗的 LARC 患者的 TIME。我们发现，预处理活检样本中肿瘤区 T 细胞亚群（CD3、CD4 和 CD8）和树突状细胞水平较高与术前 CRT 反应良好相关。CRT 后，CD3 T 细胞、CD8 T 细胞和树突状细胞的密度显著增加，而 CD4FoxP3 调节性 T 细胞的密度降低，表明 CRT 将 TIME 转变为更具免疫活性的状态。然而，CRT 通过将肿瘤相关巨噬细胞从促炎 M1 巨噬细胞极化为免疫抑制 M2 巨噬细胞，并降低 B 细胞密度，赋予了免疫抑制作用。CRT 后 CD3 T 细胞和 PD-L1 淋巴细胞的高 delta 值与良好的无病生存 (DFS) 相关，而 CD4FoxP3 调节性 T 细胞的高 delta 值与较差的 DFS 相关。这些发现为未来研究提供了一个框架，即在 LARC 患者中纳入调节 TIME 的策略。
