ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1619043
This article is part of the Research TopicCancer Immunity, Modern Radiotherapy and Immunotherapy: A Journey into Cancer Treatment InnovationView all 3 articles
Immune Activation Following PD-L1 Inhibitor Plus Chemoradiotherapy in Locally Advanced Rectal Cancer: A Retrospective, Single-Arm Study
Provisionally accepted
- 1Fourth Hospital of Hebei Medical University, Shijiazhuang, China
- 2Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
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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.: 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%).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.
Keywords: Ph: +86 15831183883 First author: Shaoqing Fan Locally advanced rectal cancer, Neoadjuvant chemoradiotherapy, Tumor Microenvironment, PD-L1 inhibitor, Tumor-infiltrating lymphocytes
Received: 27 Apr 2025; Accepted: 06 Aug 2025.
Copyright: © 2025 Fan, Zhao, Meng, Wang, Yu and Niu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wenbo Niu, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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