Fan Shaoqing, Zhao Zeming, Meng Qingyu, Wang Haiqian, Yu Bin, Niu Wenbo
Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Front Immunol. 2025 Aug 27;16:1619043. doi: 10.3389/fimmu.2025.1619043. eCollection 2025.
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.
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.
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%).
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.
局部晚期直肠癌（LARC）因复发率高和对新辅助放化疗（nCRT）反应不佳而具有挑战性。将nCRT与免疫疗法相结合可能通过改变肿瘤微环境（TME）来增强抗肿瘤免疫力。本研究评估nCRT联合程序性死亡配体1（PD-L1）抑制剂恩沃利单抗治疗LARC的疗效，并探讨其对TME的影响。
在这项回顾性单臂设计研究中，36例LARC患者（T3+/N1-2/M0）接受了卡培他滨同步长程放疗（50.4 Gy/28次分割），随后接受两个周期的XELOX化疗和恩沃利单抗治疗。术后评估病理完全缓解（pCR）和肿瘤退缩分级（TRG）。免疫组织化学分析定量配对的治疗前和治疗后肿瘤组织中CD4+、CD8+ T细胞和CD56+自然杀伤（NK）细胞浸润情况。
pCR率为47.2%（17/36），94.4%和86.1%的患者实现了原发肿瘤（T）和区域淋巴结（N）降期。治疗后肿瘤浸润淋巴细胞（TILs）增加，其中CD8+ T细胞浸润最为显著（3级：增加6例，P<0.05）。较高的基线TIL密度与更好的TRG结果相关（TRG0-2：94.4% vs. TRG3：5.6%）。
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中实现了高pCR率。这种方法在解决免疫抑制障碍的同时增强了细胞毒性免疫。进一步的研究应探索克服TME耐药的策略。
