目的:结直肠癌局部免疫反应与预后及疗效密切相关。在这项研究中,进行组织学分析以确定肿瘤浸润淋巴细胞(TIL)的表型及其在基质和肿瘤内区域的浸润,旨在阐明它们的相互作用和预后效果。
方法:使用手术切除的结直肠癌标本进行多重荧光标记,以研究CD45RO()TIL的浸润,表现出细胞毒性,和CD4(+)TIL的亚群,通过其特征性转录因子表达来鉴定。
结果:整个观察视野或基质区域的CD45RO()TIL浸润程度与预后无关。然而,肿瘤巢(肿瘤内区域)的高度浸润与良好的预后显着相关。CD4(+)TILs及其亚群与预后无关。然而,分层分析显示,基质CD4(+)TIL和T辅助(Th)1,Th2,Th17和调节性T细胞亚群的高度浸润对于高肿瘤内CD45RO(+)TIL浸润和良好预后之间的关联是必要的.
结论:肿瘤内CD45RO(+)TIL发挥对癌细胞的毒性作用需要足够程度的基质CD4(+)TIL亚群浸润。这突出了基质免疫反应在肿瘤内区域实现有效细胞毒性免疫反应中的重要性,并证明了TIL的空间分布模式在发挥其功能中的关键作用。
OBJECTIVE: The local immune response in colorectal cancer is closely related to prognosis and therapeutic efficacy. In this study, histological analyses were performed to determine the phenotype of tumor-infiltrating lymphocytes (TILs) and their infiltration in the stromal and intratumoral regions, aiming to elucidate their interactions and prognostic effects.
METHODS: Multiplex fluorescent labeling was performed using surgically resected colorectal cancer specimens to investigate the infiltration of CD45RO (+) TILs, which exhibit cytotoxicity, and subsets of CD4 (+) TILs, identified by their characteristic transcription factor expression.
RESULTS: The degree of CD45RO (+) TIL infiltration in the entire observation field or stromal area was not associated with prognosis. However, a high degree of infiltration in the tumor nest (intratumoral area) was significantly associated with a favorable prognosis. CD4 (+) TILs and their subsets were not associated with prognosis. However, stratified analyses revealed that a high degree of infiltration of stromal CD4 (+) TILs and the subsets T helper (Th)1, Th2, Th17, and regulatory T cells is necessary for the association between high intratumoral CD45RO (+) TIL infiltration and favorable prognosis.
CONCLUSIONS: A sufficient degree of infiltration of stromal CD4 (+) TIL subsets is required for intratumoral CD45RO (+) TILs to exert toxicity against cancer cells. This highlights the significance of stromal immune reactions in achieving effective cytotoxic immune responses in the intratumoral area and demonstrates the critical role of the spatial distribution pattern of TILs in exerting their functions.