The prognosis prediction value of CD69+ CD8+ tissue-resident memory T cell as a novel indicator of pathologic complete response heterogeneity following different neoadjuvant therapy regimen in esophageal squamous cell carcinoma
Abstract Background Improving pathological complete response (pCR) rate is currently the main goal of neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, improved pCR rates do not consistently translate into better prognosis, likely due to regimen-specific...
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Springer
2025-03-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-03988-3 |
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| _version_ | 1849713460463534080 |
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| author | Ao Liu Defeng Liu Xiuli Liu Yuxiang Chi Longxiang Guo Dianxing Li Qiankun Wang Yuanlin Li Yi Li Guiwen Zheng Haiqun Lin Qiuan Yang Yaru Tian Jinming Yu Minghuan Li |
| author_facet | Ao Liu Defeng Liu Xiuli Liu Yuxiang Chi Longxiang Guo Dianxing Li Qiankun Wang Yuanlin Li Yi Li Guiwen Zheng Haiqun Lin Qiuan Yang Yaru Tian Jinming Yu Minghuan Li |
| author_sort | Ao Liu |
| collection | DOAJ |
| description | Abstract Background Improving pathological complete response (pCR) rate is currently the main goal of neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, improved pCR rates do not consistently translate into better prognosis, likely due to regimen-specific pCR heterogeneity. We investigated this heterogeneity and potential biomarkers between two common neoadjuvant regimens. Methods We included 445 LA-ESCC patients from four centers, with 228 receiving neoadjuvant chemoradiotherapy (nCRT) and 217 undergoing neoadjuvant chemotherapy combined with immunotherapy (nICT). Propensity score matching ensured group comparability. We assessed pCR rates and their associations with overall survival (OS), disease-free survival (DFS), and recurrence patterns. Immune-related biomarkers were investigated through RNA sequencing and immune infiltration analysis, then validated via multiplex immunofluorescence staining. Results Overall, pCR was associated with significantly higher DFS (HR = 0.3 [0.18–0.5], P < 0.01) and OS (HR = 0.19 [0.08–0.41], P < 0.01) compared to non-pCR. The nICT group had a lower pCR rate than the nCRT group (27.2% vs. 42.9%) but demonstrated comparable prognosis and reduced distant metastasis. Among pCR patients, DFS was significantly better in the nICT group (HR = 0.2 [0.05–0.86], P = 0.031), with a trend toward improved OS. Immune analysis revealed increased CD8 + T cell infiltration, particularly CD69 + CD8 + tissue-resident memory T cells (TRM), in the nICT pCR group. The proportion of CD69 + CD8 + TRM cells was significantly linked to improved DFS (P = 0.016) and OS (P = 0.015), suggesting they may be superior prognostic markers compared to pCR rates. Conclusions The pCR obtained from different neoadjuvant treatments has distinct prognostic outcomes. The CD69 + CD8 + TRM, as a potential prognostic predictor, warrants further investigation. |
| format | Article |
| id | doaj-art-aec127a5680046e39bcaa2ddf2d9b145 |
| institution | DOAJ |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-aec127a5680046e39bcaa2ddf2d9b1452025-08-20T03:13:57ZengSpringerCancer Immunology, Immunotherapy1432-08512025-03-0174511610.1007/s00262-025-03988-3The prognosis prediction value of CD69+ CD8+ tissue-resident memory T cell as a novel indicator of pathologic complete response heterogeneity following different neoadjuvant therapy regimen in esophageal squamous cell carcinomaAo Liu0Defeng Liu1Xiuli Liu2Yuxiang Chi3Longxiang Guo4Dianxing Li5Qiankun Wang6Yuanlin Li7Yi Li8Guiwen Zheng9Haiqun Lin10Qiuan Yang11Yaru Tian12Jinming Yu13Minghuan Li14Cheeloo College of Medicine, Shandong UniversityCheeloo College of Medicine, Shandong UniversityCheeloo College of Medicine, Shandong UniversityCheeloo College of Medicine, Shandong UniversityDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Radiation Oncology, Shandong Cancer Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Radiation Oncology, Shandong Cancer Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Radiation Oncology, Shandong Cancer Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Radiation Oncology, Shandong Cancer Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Radiation Oncology, The Second Hospital of Shandong UniversityCheeloo College of Medicine, Shandong UniversityDepartment of Radiation Oncology, Shandong Cancer Hospital, Cheeloo College of Medicine, Shandong UniversityCheeloo College of Medicine, Shandong UniversityCheeloo College of Medicine, Shandong UniversityAbstract Background Improving pathological complete response (pCR) rate is currently the main goal of neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, improved pCR rates do not consistently translate into better prognosis, likely due to regimen-specific pCR heterogeneity. We investigated this heterogeneity and potential biomarkers between two common neoadjuvant regimens. Methods We included 445 LA-ESCC patients from four centers, with 228 receiving neoadjuvant chemoradiotherapy (nCRT) and 217 undergoing neoadjuvant chemotherapy combined with immunotherapy (nICT). Propensity score matching ensured group comparability. We assessed pCR rates and their associations with overall survival (OS), disease-free survival (DFS), and recurrence patterns. Immune-related biomarkers were investigated through RNA sequencing and immune infiltration analysis, then validated via multiplex immunofluorescence staining. Results Overall, pCR was associated with significantly higher DFS (HR = 0.3 [0.18–0.5], P < 0.01) and OS (HR = 0.19 [0.08–0.41], P < 0.01) compared to non-pCR. The nICT group had a lower pCR rate than the nCRT group (27.2% vs. 42.9%) but demonstrated comparable prognosis and reduced distant metastasis. Among pCR patients, DFS was significantly better in the nICT group (HR = 0.2 [0.05–0.86], P = 0.031), with a trend toward improved OS. Immune analysis revealed increased CD8 + T cell infiltration, particularly CD69 + CD8 + tissue-resident memory T cells (TRM), in the nICT pCR group. The proportion of CD69 + CD8 + TRM cells was significantly linked to improved DFS (P = 0.016) and OS (P = 0.015), suggesting they may be superior prognostic markers compared to pCR rates. Conclusions The pCR obtained from different neoadjuvant treatments has distinct prognostic outcomes. The CD69 + CD8 + TRM, as a potential prognostic predictor, warrants further investigation.https://doi.org/10.1007/s00262-025-03988-3Esophageal squamous cell carcinomaNeoadjuvantpCRImmunotherapyTissue-resident memory T cell |
| spellingShingle | Ao Liu Defeng Liu Xiuli Liu Yuxiang Chi Longxiang Guo Dianxing Li Qiankun Wang Yuanlin Li Yi Li Guiwen Zheng Haiqun Lin Qiuan Yang Yaru Tian Jinming Yu Minghuan Li The prognosis prediction value of CD69+ CD8+ tissue-resident memory T cell as a novel indicator of pathologic complete response heterogeneity following different neoadjuvant therapy regimen in esophageal squamous cell carcinoma Cancer Immunology, Immunotherapy Esophageal squamous cell carcinoma Neoadjuvant pCR Immunotherapy Tissue-resident memory T cell |
| title | The prognosis prediction value of CD69+ CD8+ tissue-resident memory T cell as a novel indicator of pathologic complete response heterogeneity following different neoadjuvant therapy regimen in esophageal squamous cell carcinoma |
| title_full | The prognosis prediction value of CD69+ CD8+ tissue-resident memory T cell as a novel indicator of pathologic complete response heterogeneity following different neoadjuvant therapy regimen in esophageal squamous cell carcinoma |
| title_fullStr | The prognosis prediction value of CD69+ CD8+ tissue-resident memory T cell as a novel indicator of pathologic complete response heterogeneity following different neoadjuvant therapy regimen in esophageal squamous cell carcinoma |
| title_full_unstemmed | The prognosis prediction value of CD69+ CD8+ tissue-resident memory T cell as a novel indicator of pathologic complete response heterogeneity following different neoadjuvant therapy regimen in esophageal squamous cell carcinoma |
| title_short | The prognosis prediction value of CD69+ CD8+ tissue-resident memory T cell as a novel indicator of pathologic complete response heterogeneity following different neoadjuvant therapy regimen in esophageal squamous cell carcinoma |
| title_sort | prognosis prediction value of cd69 cd8 tissue resident memory t cell as a novel indicator of pathologic complete response heterogeneity following different neoadjuvant therapy regimen in esophageal squamous cell carcinoma |
| topic | Esophageal squamous cell carcinoma Neoadjuvant pCR Immunotherapy Tissue-resident memory T cell |
| url | https://doi.org/10.1007/s00262-025-03988-3 |
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