■免疫检查点治疗,涉及程序性细胞死亡1(PD-1)单克隆抗体,彻底改变了癌症的治疗方法。三级淋巴结构(TLS)作为预测PD-1抗体治疗效果的免疫指标。然而,没有明确的结果是否分布,数量,TLS的成熟度可作为预测结直肠癌患者抗PD1免疫治疗临床疗效的有效指标。
■57例接受手术切除的患者和39例接受抗PD-1免疫治疗的患者被纳入这项回顾性研究。免疫组织化学染色和多重荧光免疫组织化学用于评估错配修复(MMR)亚型和TLS分布,数量,和成熟,分别。
■建立了基于TLS数量和成熟度的综合患者评分系统。我们发现,缺乏错配修复(dMMR)组的评分>1的患者比例远高于熟练错配修复(pMMR)组,这种差异主要是由于肿瘤内TLS。患者评分,基于对整个肿瘤的TLS评估,perumor,或瘤内,用于评估抗PD1免疫疗法的疗效。仅基于肿瘤内TLS评估,评分>1的患者比例在缓解(PR+CR)组中高于无缓解(PD)组.多因素分析显示患者评分与免疫治疗的临床疗效呈正相关。对接受抗PD-1免疫疗法的CRC患者进行了免疫相关的无进展生存期的进一步分析。基于肿瘤内TLS评估的评分>1的患者具有显著更好的生存率。
■这些结果表明,基于肿瘤内TLS评估的患者评分可能是CRC患者PD-1抗体治疗的良好免疫预测指标。
Immune checkpoint therapy, involving the programmed cell death 1 (PD-1) monoclonal antibody, has revolutionized the treatment of cancer. Tertiary lymphatic structure (TLS) serves as an immune indicator to predict the efficacy of PD-1 antibody therapy. However, there is no clear result whether the distribution, quantity, and maturity of TLS can be effective indicators for predicting the clinical efficacy of anti-PD1 immunotherapy in patients with colorectal cancer (CRC).
Fifty-seven patients who underwent surgical resection and thirty-nine patients who received anti-PD-1 immunotherapy were enrolled in this retrospective study. Immunohistochemical staining and multiple fluorescence immunohistochemistry were used to evaluate the mismatch repair (MMR) subtypes and TLS distribution, quantity, and maturity, respectively.
A comprehensive patient score system was built based on TLS quantity and maturity. We found that the proportion of patients with score >1 was much higher in the deficient mismatch repair(dMMR) group than in the proficient mismatch repair(pMMR) group, and this difference was mainly due to intratumoral TLS. Patient score, based on the TLS evaluation of whole tumor, peritumor, or intratumor, was used to evaluate the efficacy of anti-PD1 immunotherapy. Based only on the intratumor TLS evaluation, the proportion of patients with a score >1 was higher in the response (PR + CR) group than in the non-response (PD) group. Multivariate analysis revealed that patient scores were positively correlated with the clinical efficacy of immunotherapy. Further analysis of immune-related progression-free survival was performed in patients with CRC who received anti-PD-1 immunotherapy. Patients with score >1 based on the intratumor TLS evaluation had significantly better survival.
These results suggest that the patient score based on intratumor TLS evaluation may be a good immune predictive indicator for PD-1 antibody therapy in patients with CRC.