Immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancer
BackgroundThe therapeutic efficacy of neoadjuvant immunotherapy combined with chemotherapy (Io+Chemo) is superior than chemotherapy alone (Chemo). However, the mechanism of Io+Chemo superiority remains to be further elucidated.MethodsThe study included 128 patients with resectable stage II-III gastr...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1497004/full |
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| author | Ning Zhang Chunyu Li Zehua Zhao Biying Jiang Wentao Wang Fujing Sun Yong Zhang Yanmei Zhu |
| author_facet | Ning Zhang Chunyu Li Zehua Zhao Biying Jiang Wentao Wang Fujing Sun Yong Zhang Yanmei Zhu |
| author_sort | Ning Zhang |
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| description | BackgroundThe therapeutic efficacy of neoadjuvant immunotherapy combined with chemotherapy (Io+Chemo) is superior than chemotherapy alone (Chemo). However, the mechanism of Io+Chemo superiority remains to be further elucidated.MethodsThe study included 128 patients with resectable stage II-III gastric cancer, in which 63 were given neoadjuvant Io+Chemo, and 65 Chemo alone. Patients given Io+Chemo were treated with 2-4 cycles of PD-(L)1 inhibitor (Pembrolizumab, Sintililimab or Nivolumab) with S-1 and oxaliplatin (SOX) or capecitabine and oxaliplatin (XELOX) before surgical resection. Patients given Chemo were treated with 2-4 cycles of SOX or XELOX before surgical resection. Tumor tissues were evaluated for tumor-infiltrating immune cells (TIICs) using immunohistochemistry and QuPath software quantitative analysis, for detecting T, B, NK, plasma cells, and macrophages. The relationship between TIICs and different neoadjuvant treatment regimens and pathological responses was also explored.ResultsCompared with Chemo, Io+Chemo induced higher rates of pathological complete response (33.3 vs. 9.2%, p=0.001) and major pathological response (MPR) (49.2 vs. 30.8%, p=0.033). Compared with Chemo group, density of CD4+(1904.8 vs. 1530), CD8+(1982.9 vs. 1124.4), CD20+(1115.6 vs. 574), CD38+(1580.4 vs. 1128), CD138+(1237.2 vs. 496.4), and CD56+ (596.8 vs. 159) cells was increased 24.5%, 76.4%, 94.4%, 40.1%, and 149.2% respectively, whereas CD163+ macrophages (994.4 vs. 1706) was decreased 41.7% in Io+Chemo group.ConclusionsOur study favors neoadjuvant Io+Chemo over Chemo and reveals Io+Chemo can induce the formation of an immune-activated microenvironment that make Io+Chemo superior to Chemo. |
| format | Article |
| id | doaj-art-99c66c24db5c4b2b8ff36861a353ffd5 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-99c66c24db5c4b2b8ff36861a353ffd52025-01-27T06:40:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.14970041497004Immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancerNing Zhang0Chunyu Li1Zehua Zhao2Biying Jiang3Wentao Wang4Fujing Sun5Yong Zhang6Yanmei Zhu7Department of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, ChinaDepartment of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, ChinaDepartment of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, ChinaDepartment of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, ChinaDepartment of Gastric Surgery, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, ChinaDepartment of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, ChinaDepartment of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, ChinaDepartment of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, ChinaBackgroundThe therapeutic efficacy of neoadjuvant immunotherapy combined with chemotherapy (Io+Chemo) is superior than chemotherapy alone (Chemo). However, the mechanism of Io+Chemo superiority remains to be further elucidated.MethodsThe study included 128 patients with resectable stage II-III gastric cancer, in which 63 were given neoadjuvant Io+Chemo, and 65 Chemo alone. Patients given Io+Chemo were treated with 2-4 cycles of PD-(L)1 inhibitor (Pembrolizumab, Sintililimab or Nivolumab) with S-1 and oxaliplatin (SOX) or capecitabine and oxaliplatin (XELOX) before surgical resection. Patients given Chemo were treated with 2-4 cycles of SOX or XELOX before surgical resection. Tumor tissues were evaluated for tumor-infiltrating immune cells (TIICs) using immunohistochemistry and QuPath software quantitative analysis, for detecting T, B, NK, plasma cells, and macrophages. The relationship between TIICs and different neoadjuvant treatment regimens and pathological responses was also explored.ResultsCompared with Chemo, Io+Chemo induced higher rates of pathological complete response (33.3 vs. 9.2%, p=0.001) and major pathological response (MPR) (49.2 vs. 30.8%, p=0.033). Compared with Chemo group, density of CD4+(1904.8 vs. 1530), CD8+(1982.9 vs. 1124.4), CD20+(1115.6 vs. 574), CD38+(1580.4 vs. 1128), CD138+(1237.2 vs. 496.4), and CD56+ (596.8 vs. 159) cells was increased 24.5%, 76.4%, 94.4%, 40.1%, and 149.2% respectively, whereas CD163+ macrophages (994.4 vs. 1706) was decreased 41.7% in Io+Chemo group.ConclusionsOur study favors neoadjuvant Io+Chemo over Chemo and reveals Io+Chemo can induce the formation of an immune-activated microenvironment that make Io+Chemo superior to Chemo.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1497004/fullgastric cancertumor-infiltrating immune cellstumor immune microenvironmentneoadjuvant therapyimmunochemotherapy |
| spellingShingle | Ning Zhang Chunyu Li Zehua Zhao Biying Jiang Wentao Wang Fujing Sun Yong Zhang Yanmei Zhu Immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancer Frontiers in Immunology gastric cancer tumor-infiltrating immune cells tumor immune microenvironment neoadjuvant therapy immunochemotherapy |
| title | Immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancer |
| title_full | Immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancer |
| title_fullStr | Immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancer |
| title_full_unstemmed | Immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancer |
| title_short | Immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancer |
| title_sort | immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancer |
| topic | gastric cancer tumor-infiltrating immune cells tumor immune microenvironment neoadjuvant therapy immunochemotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1497004/full |
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