肿瘤细胞治疗研究
英文原题：Total neoadjuvant chemotherapy combined with PD‑1 blockade and IL‑2 in MSS/pMMR locally advanced rectal cancer: short-term results of a prospective, single-arm phase II study.
共纳入33例患者，年龄18-75岁，直肠肿瘤位于距肛缘12 cm以内，分期为cT3/4N_anyM0或cT_anyN⁺M0。
新辅助治疗已成为局部晚期直肠癌（LARC）管理的基石。在这项单臂、开放标签的II期研究中，我们评估了使用CapOX方案联合程序性细胞死亡蛋白1（PD-1）抗体（信迪利单抗）和白细胞介素-2（IL-2）的全新辅助化疗（TNT）在微卫星稳定（MSS）/错配修复功能完整（pMMR）LARC患者中的疗效和安全性。共纳入33例患者，年龄18-75岁，直肠肿瘤位于距肛缘12 cm以内，分期为cT3/4N_anyM0或cT_anyN⁺M0。患者接受由奥沙利铂、信迪利单抗、卡培他滨和IL-2组成的方案，以三周为一个周期给药，每两个周期后进行疗效评估。完成六个周期治疗后，33例患者接受了根治性手术，R0切除率为100%。病理完全缓解（pCR）率为42.4%（95% CI：25.68-59.16%），其余19例患者（57.6%，95% CI：41.07-74.09%）被评估为部分缓解。肿瘤退缩分级（TRG）分别为：TRG1：3例（9.1%，95% CI：1.90-25.97%），TRG2：14例（42.4%，95% CI：26.27-60.38%），TRG3：2例（6.1%，95% CI：0.73-20.37%）。手术安全性方面，未报告B/C级吻合口漏或肠梗阻病例。不良事件（AEs）可控，3级事件发生率为21.2%，无IV/V级事件或治疗相关死亡。中位随访25.5周，未观察到复发。对不同治疗结局患者的血液和组织样本分析显示，达到pCR的患者肿瘤微环境中CD8+ T细胞、NK细胞和M1巨噬细胞亚群显著激活。这些令人信服的数据表明，在MSS/pMMR LARC中，该方案具有令人鼓舞的疗效和良好的安全性特征。这些发现值得进一步开展研究，以验证该方案作为直肠癌新型治疗范式的价值。ClinicalTrials.gov注册号：NCT06108596。
Neoadjuvant therapy has become a cornerstone in the management of locally advanced rectal cancer (LARC). In this single-arm, open-label phase II study, we evaluated the efficacy and safety of total neoadjuvant chemotherapy (TNT) using a CapOX regimen combined with a programmed cell death protein 1 (PD‑1) antibody (sintilimab) and interleukin‑2 (IL‑2) in patients with microsatellite stable (MSS)/defining proficient mismatch repair (pMMR) LARC. A total of 33 patients, aged 18-75 years, with rectal tumors located within 12 cm from the anal verge and staged as cT3/4N_anyM0 or cT_anyN⁺M0, were enrolled. Patients received a regimen consisting of oxaliplatin, sintilimab, capecitabine, and IL‑2 administered in a three‑week cycle, with response evaluations performed after every two cycles. Following six cycles of treatment, 33 patients underwent radical surgery, achieving a 100% R0 resection rate. The pathological complete response (pCR) rate was 42.4% (95% CI: 25.68-59.16%) while the remaining 19 patients (57.6%, 95% CI: 41.07-74.09%) were assessed as having a partial response. The tumor regression grades (TRG) were, TRG1: 3 cases (9.1%, 95% CI: 1.90-25.97%), TRG2: 14 cases (42.4%, 95% CI: 26.27-60.38%), and TRG3: 2 cases (6.1%, 95% CI: 0.73-20.37%), respectively. Surgical safety reported as no cases of grade B/C anastomotic leakage or bowel obstruction. Adverse events (AEs) were manageable, with a 21.2% incidence of grade 3 events and no grade IV/V events or treatment‑related deaths. With a median follow‑up of 25.5 weeks, no recurrences were observed. Analysis of blood and tissue samples from patients with different treatment outcomes revealed significant activation of CD8 + T cells, NK cells, and M1 macrophage subsets in the tumor microenvironment of patients achieving pCR. These compelling data demonstrate promising efficacy with a favorable safety profile in MSS/pMMR LARC. These findings warrant studies to validate this regimen as a novel treatment paradigm for rectal cancer. ClinicalTrials.gov registration: NCT06108596.
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