Low-exhaustion peripheral circulating γδ T cells serve as a biomarker for predicting the clinical benefit rate of non-small cell lung cancer (NSCLC) patients to chemotherapy or targeted therapy: a single-center retrospective study
Abstract Background Multiple studies have demonstrated that the abundance and functionality of γδ T cells are favorable prognostic indicators for prolonged survival in cancer patients. However, the association between the immunophenotype of circulating γδ T cells and the therapeutic response in NSCL...
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BMC
2025-01-01
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| Online Access: | https://doi.org/10.1186/s12885-025-13497-2 |
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| author | Dongdong Zhang Guichao Liu Jinhui Ye Ke Li Guojun Zhang Qiang Quan Xinhai Zhu Peng Li |
| author_facet | Dongdong Zhang Guichao Liu Jinhui Ye Ke Li Guojun Zhang Qiang Quan Xinhai Zhu Peng Li |
| author_sort | Dongdong Zhang |
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| description | Abstract Background Multiple studies have demonstrated that the abundance and functionality of γδ T cells are favorable prognostic indicators for prolonged survival in cancer patients. However, the association between the immunophenotype of circulating γδ T cells and the therapeutic response in NSCLC patients undergoing chemotherapy or targeted therapy remains unclear. Methods Patients with EGFR wild-type (EGFR-WT) or mutant (EGFR-Mut) non-small cell lung cancer (NSCLC), diagnosed between January 2020 and January 2024, were included in this study. Clinicopathological characteristics, treatment regimens, and follow-up data were retrospectively collected. Peripheral blood samples from 52 NSCLC patients were analyzed for the immunophenotypes of αβ T cells and γδ T cells using full-spectrum flow cytometry. Results No significant differences were observed in the proportions of αβ T cells or γδ T cells, nor in the expression of immune exhaustion markers, between epidermal growth factor receptor wild-type and mutant NSCLC patients. Notably, NSCLC patients with a high clinical benefit rate (responder, R) exhibited a higher proportion of circulating Vδ2 T cells compared to non-responders (NR), in both EGFR-Mut (NR vs. R, P = 0.0437) and EGFR-WT groups (NR vs. R, P = 0.0180). Additionally, the expression of the immune exhaustion marker PD-1 on Vδ2 T cells was significantly lower in the responder group (NR vs. R, EGFR-Mut, P = 0.0050; EGFR-WT, P = 0.0180). Moreover, responder patients exhibited elevated levels of TNF-α compared to non-responders, irrespective of EGFR mutation status (NR vs. R, EGFR-Mut, P = 0.0055; EGFR-WT, P = 0.0007). Conclusions These findings collectively suggest that circulating Vδ2 T cells with low levels of immune exhaustion are critical contributors to the effectiveness of chemotherapy and targeted therapies in NSCLC. Targeting Vδ2 T cells may represent a promising strategy for enhancing therapeutic clinical benefit rates in NSCLC patients. |
| format | Article |
| id | doaj-art-3d36042a20884798afb915f8a0d80528 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-3d36042a20884798afb915f8a0d805282025-02-02T12:29:03ZengBMCBMC Cancer1471-24072025-01-0125111110.1186/s12885-025-13497-2Low-exhaustion peripheral circulating γδ T cells serve as a biomarker for predicting the clinical benefit rate of non-small cell lung cancer (NSCLC) patients to chemotherapy or targeted therapy: a single-center retrospective studyDongdong Zhang0Guichao Liu1Jinhui Ye2Ke Li3Guojun Zhang4Qiang Quan5Xinhai Zhu6Peng Li7Department of Thoracic Surgery, The First Affiliated Hospital, Jinan UniversityDepartment of Oncology, Research Center of Cancer Diagnosis and Therapy, The First Affiliated Hospital, Jinan UniversityDepartment of Breast Oncology, The First People’s Hospital of ZhaoqingDepartment of Geriatrics, The Seventh Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Oncology, Research Center of Cancer Diagnosis and Therapy, The First Affiliated Hospital, Jinan UniversityDepartment of Oncology, Research Center of Cancer Diagnosis and Therapy, The First Affiliated Hospital, Jinan UniversityDepartment of Oncology, Research Center of Cancer Diagnosis and Therapy, The First Affiliated Hospital, Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan UniversityAbstract Background Multiple studies have demonstrated that the abundance and functionality of γδ T cells are favorable prognostic indicators for prolonged survival in cancer patients. However, the association between the immunophenotype of circulating γδ T cells and the therapeutic response in NSCLC patients undergoing chemotherapy or targeted therapy remains unclear. Methods Patients with EGFR wild-type (EGFR-WT) or mutant (EGFR-Mut) non-small cell lung cancer (NSCLC), diagnosed between January 2020 and January 2024, were included in this study. Clinicopathological characteristics, treatment regimens, and follow-up data were retrospectively collected. Peripheral blood samples from 52 NSCLC patients were analyzed for the immunophenotypes of αβ T cells and γδ T cells using full-spectrum flow cytometry. Results No significant differences were observed in the proportions of αβ T cells or γδ T cells, nor in the expression of immune exhaustion markers, between epidermal growth factor receptor wild-type and mutant NSCLC patients. Notably, NSCLC patients with a high clinical benefit rate (responder, R) exhibited a higher proportion of circulating Vδ2 T cells compared to non-responders (NR), in both EGFR-Mut (NR vs. R, P = 0.0437) and EGFR-WT groups (NR vs. R, P = 0.0180). Additionally, the expression of the immune exhaustion marker PD-1 on Vδ2 T cells was significantly lower in the responder group (NR vs. R, EGFR-Mut, P = 0.0050; EGFR-WT, P = 0.0180). Moreover, responder patients exhibited elevated levels of TNF-α compared to non-responders, irrespective of EGFR mutation status (NR vs. R, EGFR-Mut, P = 0.0055; EGFR-WT, P = 0.0007). Conclusions These findings collectively suggest that circulating Vδ2 T cells with low levels of immune exhaustion are critical contributors to the effectiveness of chemotherapy and targeted therapies in NSCLC. Targeting Vδ2 T cells may represent a promising strategy for enhancing therapeutic clinical benefit rates in NSCLC patients.https://doi.org/10.1186/s12885-025-13497-2γδ T cellImmune exhaustionNSCLCChemotherapyTargeted therapy |
| spellingShingle | Dongdong Zhang Guichao Liu Jinhui Ye Ke Li Guojun Zhang Qiang Quan Xinhai Zhu Peng Li Low-exhaustion peripheral circulating γδ T cells serve as a biomarker for predicting the clinical benefit rate of non-small cell lung cancer (NSCLC) patients to chemotherapy or targeted therapy: a single-center retrospective study BMC Cancer γδ T cell Immune exhaustion NSCLC Chemotherapy Targeted therapy |
| title | Low-exhaustion peripheral circulating γδ T cells serve as a biomarker for predicting the clinical benefit rate of non-small cell lung cancer (NSCLC) patients to chemotherapy or targeted therapy: a single-center retrospective study |
| title_full | Low-exhaustion peripheral circulating γδ T cells serve as a biomarker for predicting the clinical benefit rate of non-small cell lung cancer (NSCLC) patients to chemotherapy or targeted therapy: a single-center retrospective study |
| title_fullStr | Low-exhaustion peripheral circulating γδ T cells serve as a biomarker for predicting the clinical benefit rate of non-small cell lung cancer (NSCLC) patients to chemotherapy or targeted therapy: a single-center retrospective study |
| title_full_unstemmed | Low-exhaustion peripheral circulating γδ T cells serve as a biomarker for predicting the clinical benefit rate of non-small cell lung cancer (NSCLC) patients to chemotherapy or targeted therapy: a single-center retrospective study |
| title_short | Low-exhaustion peripheral circulating γδ T cells serve as a biomarker for predicting the clinical benefit rate of non-small cell lung cancer (NSCLC) patients to chemotherapy or targeted therapy: a single-center retrospective study |
| title_sort | low exhaustion peripheral circulating γδ t cells serve as a biomarker for predicting the clinical benefit rate of non small cell lung cancer nsclc patients to chemotherapy or targeted therapy a single center retrospective study |
| topic | γδ T cell Immune exhaustion NSCLC Chemotherapy Targeted therapy |
| url | https://doi.org/10.1186/s12885-025-13497-2 |
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