新辅助放化疗对局部进展期直肠癌疗效及肿瘤免疫微环境变化的研究

Neoadjuvant chemoradiotherapy for treatment of locally advanced rectal cancer:Efficacy and tumor immune microenvironment changes

目的探讨直肠癌新辅助治疗前后肿瘤组织中CD4^(+)、CD8^(+)淋巴细胞的变化及TIL密度的变化,寻找术前新辅助放化疗敏感的免疫标志物。方法通过核磁及术后病理对比52例直肠癌患者经过新辅助治疗后的分期变化及疗效评价,采用免疫组化的方法评价新辅助放化疗前后肿瘤组织的CD4^(+)、CD8^(+)T细胞数量的变化。结果CD4^(+)T细胞数量在放疗后TIL1级中增加2例,TIL2级中增加1例,TIL3级中减少3例。放疗前后CD4^(+)TIL分级对比差异无统计学意义(P>0.05)。CD8^(+)T细胞数量在放疗后TIL1级中减少10例,TIL2级中增加6例,TIL3级中增加4例。放疗前后CD8^(+)TIL分级对比差异有统计学意义(P<0.05)。放疗前直肠癌肿瘤组织中CD8^(+)TIL密度越高,患者出现CR和PR的比例越多,SD和PD例数越少,对比有统计学差异(P<0.05)。放疗前直肠癌肿瘤组织中CD4^(+)TIL密度与肿瘤组织局部疗效的关系,两者之间差异无统计学意义(P>0.05)。结论直肠癌经术前新辅助放化疗治疗后,肿瘤T分期降期率为46.2%,N分期降期率为40.4%。CD8^(+)T细胞在直肠癌放化疗后肿瘤组织中明显增多,而CD4^(+)T细胞没有明显变化。CD8^(+)T细胞TIL分级越高,术后肿瘤退缩率越高,CD+T细胞TIL分级可能是预测放疗敏感性的预测指标。

Objective To investigate the changes of CD4^(+)and CD8^(+)T lymphocyte subsets and tumorinfiltrating lymphocyte(TIL)density in tumor tissue before and after neoadjuvant treatment for rectal cancer,and to find immune markers for sensitivity to preoperative neoadjuvant chemoradiotherapy.Methods The stage changes and efficacy evaluation after neoadjuvant therapy were assessed by magnetic resonance imaging and pathology.The number of CD4^(+)and CD8^(+)T cells in tumor tissue before and after neoadjuvant radiotherapy and chemotherapy was assessed by immunohistochemistry.Results After radiotherapy,there were two more cases of CD4^(+)TIL grade 1,one more case of CD4^(+)TIL grade 2,and three less cases of CD4^(+)TIL grade 3.There was no statistically significant difference in the CD4^(+)TIL grade distribution between before and after radiotherapy(P>0.05).After radiotherapy,there were ten less cases of CD8^(+)TIL grade 1,six more cases of CD8^(+)TIL grade 2,and four more cases of CD8^(+)TIL grade 3.There was a statistically significant difference in the CD8^(+)TIL grade distribution between before and after radiotherapy(P<0.05).The higher the CD8^(+)TIL density in rectal cancer tumor tissue before radiotherapy,the more the proportion of patients achieving complete remission and partial remission,and the less the number of cases with stable disease and progressive disease(P<0.05).There was no significant correlation between CD4^(+)TIL density and the local efficacy(P>0.05).Conclusion After neoadjuvant radiotherapy and chemotherapy for rectal cancer,the reduction rate of T stage cases is 46.2%,and that of N stage is 40.4%.CD8^(+)T cells significantly increase in tumor tissue after chemoradiotherapy for rectal cancer,but there are no significant changes in CD4^(+)T cells.Higher CD8^(+)TIL grade is associated with a higher postoperative tumor regression rate.CD8^(+)TIL grade may be a predictive indicator for radiation sensitivity.