摘要
背景:研究认为,淋巴细胞密度与直肠癌预后相关;但新辅助治疗前淋巴细胞分布模式对预后的影响尚不清楚。本研究旨在评估淋巴细胞的分布及密度与直肠癌新辅助治疗反应的关系。方法:对前瞻性队列中接受新辅助治疗的134例直肠癌患者进行回顾性分析。对新辅助治疗前活检标本进行免疫组化染色(CD4和CD8)。评估瘤内腺体周围淋巴细胞(IPL)和肿瘤浸润淋巴细胞(TIL)的密度。采用logistic回归模型(包括临床病理特征、分子特征及治疗方案)评估不同淋巴细胞的密度与肿瘤退缩分级(TRG)的关系。结果:CD8^(+)TIL密度高的患者接受新辅助治疗后获得了更佳的TRG(OR=0.23,95%CI:0.07-0.76,P<0.001)。而CD8^(+)IPL(P=0.033)、CD4^(+)IPL(P=0.156)和CD4^(+)TIL(P=0.170)则与TRG无明显相关性。敏感性分析未发现CD8^(+)TIL与新辅助放疗(P_(相互作用)=0.831)或化疗(P_(交互作用)=0.879)对TRG的影响存在交互作用。结论:本研究结果显示,CD8^(+)TIL而不是CD8^(+)IPL,可独立影响直肠癌新辅助治疗反应,这种影响不受放疗或化疗方案的干扰。
Background:Lymphocytic density in rectal cancer has been reported to be associated with therapeutic response,but the role of the lymphocytic distribution pattern remains to be determined.This study aimed to evaluate the association between the distribution and density of lymphocytes in rectal-cancer tissue with tumor response to neoadjuvant therapy.Methods:We retrospectively analysed 134 patients with rectal cancer receiving neoadjuvant therapy within a prospectively maintained cohort.Pretherapeutic biopsy samples were stained with immunohistochemistry(CD4 and CD8).Densities of intratumoral periglandular lymphocytes(IPLs)and tumor-infiltrating lymphocytes(TILs)were assessed separately.Logistic-regression analysis was used to assess associations of lymphocyte densities with tumor regression grade(TRG),controlling for clinicopathological,molecular,and regimen features.Results:Compared with cases in the lowest quartile of CD8^(+)TILs,those in the highest quartile were significantly associated with better TRG(multivariate odds ratio,0.23;95%confidence interval,0.07 to 0.76;P<0.001).In contrast,CD8^(+)IPLs,CD4^(+)IPLs,and CD4^(+)TILswere not significantly associatedwith TRG(P=0.033,0.156,and 0.170,respectively).Sensitivity analyses detected no interaction between CD8^(+)TILs and regimen of neoadjuvant radiation(Pinteraction=0.831)or chemotherapy(Pinteraction=0.879)on TRG.Conclusions:Our data suggest that CD8^(+)TILs,but not IPLs,are independently associated with response to neoadjuvant therapy,regardless of the regimen of radiation or chemotherapy.
基金
supported by a National Natural Scientific Foundation of China grant[No.31601077 to R.D.]
a Guangzhou Science and Technology Plan[No.201604020005 to J.W.].
