研究概要
nCRT 联合恩沃利单抗可增强免疫细胞浸润,尤其是 CD8⁺ T 细胞,在 LARC 中取得高 pCR 率。
中文摘要
背景:局部晚期直肠癌(LARC)复发率高且新辅助放化疗(nCRT)应答不佳,治疗难度大。nCRT联合免疫疗法可能通过改变肿瘤微环境(TME)增强抗肿瘤免疫。本研究评估nCRT联合PD-L1抑制剂envafolimab治疗LARC的疗效,并探究其对TME的影响。
方法:本回顾性单臂研究纳入36例LARC患者(T3+/N1-2/M0),接受长程放射治疗(50.4 Gy/28次)联合卡培他滨,随后接受2个周期XELOX化疗及envafolimab。术后评估病理完全缓解(pCR)和肿瘤退缩分级(TRG)。通过免疫组织化学定量分析治疗前后配对肿瘤组织中的CD4+、CD8+ T细胞和CD56+ NK细胞浸润。
结果:pCR率为47.2%(17/36),T分期和N分期降期率分别为94.4%和86.1%。治疗后TIL(肿瘤浸润淋巴细胞)增加,其中CD8+ T细胞浸润增加最显著(3级:增加6例,P<0.05)。基线TIL密度较高与更好的TRG结局相关(TRG0–2:94.4%;TRG3:5.6%)。
结论:nCRT联合envafolimab可增强免疫细胞浸润,尤其是CD8+ T细胞浸润,并使LARC患者达到较高pCR率。该方案可增强细胞毒性免疫,同时应对免疫抑制屏障。未来研究应探索克服TME耐药的策略。
展开英文摘要原文
BACKGROUND: Locally advanced rectal cancer (LARC) is challenging due to high recurrence rates and poor responses to neoadjuvant chemoradiotherapy (nCRT). Combining nCRT with immunotherapy may enhance antitumor immunity by modifying the tumor microenvironment (TME). This study evaluates the efficacy of nCRT with PD-L1 inhibitor envafolimab in LARC and explores its impact on TME.
METHODS: In this retrospective, single-arm design study, 36 LARC patients (T3+/N1-2/M0) received long-course radiotherapy (50.4 Gy/28 fractions) with capecitabine, followed by two cycles of XELOX chemotherapy and envafolimab. Pathological complete response (pCR) and tumor regression grade (TRG) were assessed post-surgery. Immunohistochemical analysis quantified CD4+, CD8+ T cells, and CD56+ NK cell infiltration in paired pre- and post-treatment tumor tissues.
RESULTS: The pCR rate was 47.2% (17/36), with 94.4% and 86.1% achieving T- and N-downstaging. Post-treatment tumor-infiltrating lymphocytes (TILs) increased, with CD8+ T cells showing the most significant infiltration (Grade 3: +6 cases, P<0.05). Higher baseline TIL density correlated with better TRG outcomes (TRG0-2: 94.4% vs. TRG3: 5.6%).
CONCLUSION: nCRT combined with envafolimab enhances immune cell infiltration, particularly CD8+ T cells, achieving high pCR rates in LARC. This approach enhances cytotoxic immunity while addressing immunosuppressive barriers. Further studies should explore strategies to overcome TME resistance.
论文信息
- 作者
- Fan S、Zhao Z、Meng Q、Wang H、Yu B、Niu W
- 单位
- Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.China
- 期刊
- Frontiers in immunology2025