Peripheral EBV antigen-specific T cell is dysfunctional in Epstein–Barr virus positive diffuse large B-cell lymphoma
Abstract EBV-positive diffuse large B-cell lymphoma (EBV + DLBCL) is associated with poor prognosis, possibly due to the capacity of EBV to dampen host anti-tumor immunity. Patients’ peripheral EBV antigen-specific T lymphocytes may be functional deficiency. This study investigated the mechanisms un...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-08-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-025-14723-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849764400801513472 |
|---|---|
| author | Liang Gao Lihong Wang Chao Xue Xinan Cen |
| author_facet | Liang Gao Lihong Wang Chao Xue Xinan Cen |
| author_sort | Liang Gao |
| collection | DOAJ |
| description | Abstract EBV-positive diffuse large B-cell lymphoma (EBV + DLBCL) is associated with poor prognosis, possibly due to the capacity of EBV to dampen host anti-tumor immunity. Patients’ peripheral EBV antigen-specific T lymphocytes may be functional deficiency. This study investigated the mechanisms underlying this deficiency by examining the phenotypes and function of peripheral T cells via ELISPOT and flow cytometry. 6 EBV + DLBCL patients, 54 EBV-negative DLBCL (EBV- DLBCL) patients, and 12 healthy controls were enrolled. We observed significantly reduced IFN-γ secreting T cells in EBV + patients upon EBV peptides stimulation compared to EBV-negative patients (P < 0.001), indicating a dysfunction in EBV antigen-specific T cells. Furtherly, compared to EBV- DLBCL, EBV + DLBCL showed decreased proportions of total lymphocytes (P = 0.005), CD8+ T cells (P = 0.004), CD4+ T cells central memory (P = 0.017), CD8+ T cells naïve (P = 0.001), and CD8+ T cells effector (P = 0.031), alongside increased CD4+ and CD8+ effector memory T cells (P = 0.010 and P < 0.001, respectively). Both CD4+ and CD8+ T cells demonstrated elevated PD-1 expression (P = 0.045 and P = 0.036, respectively), and the CD4+TIM-3−CTLA-4− population was reduced (P = 0.049), in EBV + DLBCL. There was also a significant decline in CD28+KLRG1− (P = 0.018) and CD28+CD57−KLRG1− (P = 0.036) subsets among CD8+ T cells in EBV + patients. CD8+ T cells showed decreased IFN-γ expression after PMA/BFA stimulation in EBV + DLBCL(P = 0.015). These findings suggested that EBV antigen-specific T cell functional deficits might correlate with altered T cell subset distributions, heightened levels of exhaustion and senescence, and diminished expression of immune effector molecules. |
| format | Article |
| id | doaj-art-fbdbf4f3b0f04aebb35b77d85573b3e6 |
| institution | DOAJ |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-fbdbf4f3b0f04aebb35b77d85573b3e62025-08-20T03:05:09ZengBMCBMC Cancer1471-24072025-08-0125111610.1186/s12885-025-14723-7Peripheral EBV antigen-specific T cell is dysfunctional in Epstein–Barr virus positive diffuse large B-cell lymphomaLiang Gao0Lihong Wang1Chao Xue2Xinan Cen3Department of Geriatrics, Peking University First HospitalDepartment of Hematology, Peking University First HospitalDepartment of Hematology, Peking University First HospitalDepartment of Hematology, Peking University First HospitalAbstract EBV-positive diffuse large B-cell lymphoma (EBV + DLBCL) is associated with poor prognosis, possibly due to the capacity of EBV to dampen host anti-tumor immunity. Patients’ peripheral EBV antigen-specific T lymphocytes may be functional deficiency. This study investigated the mechanisms underlying this deficiency by examining the phenotypes and function of peripheral T cells via ELISPOT and flow cytometry. 6 EBV + DLBCL patients, 54 EBV-negative DLBCL (EBV- DLBCL) patients, and 12 healthy controls were enrolled. We observed significantly reduced IFN-γ secreting T cells in EBV + patients upon EBV peptides stimulation compared to EBV-negative patients (P < 0.001), indicating a dysfunction in EBV antigen-specific T cells. Furtherly, compared to EBV- DLBCL, EBV + DLBCL showed decreased proportions of total lymphocytes (P = 0.005), CD8+ T cells (P = 0.004), CD4+ T cells central memory (P = 0.017), CD8+ T cells naïve (P = 0.001), and CD8+ T cells effector (P = 0.031), alongside increased CD4+ and CD8+ effector memory T cells (P = 0.010 and P < 0.001, respectively). Both CD4+ and CD8+ T cells demonstrated elevated PD-1 expression (P = 0.045 and P = 0.036, respectively), and the CD4+TIM-3−CTLA-4− population was reduced (P = 0.049), in EBV + DLBCL. There was also a significant decline in CD28+KLRG1− (P = 0.018) and CD28+CD57−KLRG1− (P = 0.036) subsets among CD8+ T cells in EBV + patients. CD8+ T cells showed decreased IFN-γ expression after PMA/BFA stimulation in EBV + DLBCL(P = 0.015). These findings suggested that EBV antigen-specific T cell functional deficits might correlate with altered T cell subset distributions, heightened levels of exhaustion and senescence, and diminished expression of immune effector molecules.https://doi.org/10.1186/s12885-025-14723-7EBV-positive DLBCLT cell dysfunctionT cell exhaustionT cell senescence |
| spellingShingle | Liang Gao Lihong Wang Chao Xue Xinan Cen Peripheral EBV antigen-specific T cell is dysfunctional in Epstein–Barr virus positive diffuse large B-cell lymphoma BMC Cancer EBV-positive DLBCL T cell dysfunction T cell exhaustion T cell senescence |
| title | Peripheral EBV antigen-specific T cell is dysfunctional in Epstein–Barr virus positive diffuse large B-cell lymphoma |
| title_full | Peripheral EBV antigen-specific T cell is dysfunctional in Epstein–Barr virus positive diffuse large B-cell lymphoma |
| title_fullStr | Peripheral EBV antigen-specific T cell is dysfunctional in Epstein–Barr virus positive diffuse large B-cell lymphoma |
| title_full_unstemmed | Peripheral EBV antigen-specific T cell is dysfunctional in Epstein–Barr virus positive diffuse large B-cell lymphoma |
| title_short | Peripheral EBV antigen-specific T cell is dysfunctional in Epstein–Barr virus positive diffuse large B-cell lymphoma |
| title_sort | peripheral ebv antigen specific t cell is dysfunctional in epstein barr virus positive diffuse large b cell lymphoma |
| topic | EBV-positive DLBCL T cell dysfunction T cell exhaustion T cell senescence |
| url | https://doi.org/10.1186/s12885-025-14723-7 |
| work_keys_str_mv | AT lianggao peripheralebvantigenspecifictcellisdysfunctionalinepsteinbarrviruspositivediffuselargebcelllymphoma AT lihongwang peripheralebvantigenspecifictcellisdysfunctionalinepsteinbarrviruspositivediffuselargebcelllymphoma AT chaoxue peripheralebvantigenspecifictcellisdysfunctionalinepsteinbarrviruspositivediffuselargebcelllymphoma AT xinancen peripheralebvantigenspecifictcellisdysfunctionalinepsteinbarrviruspositivediffuselargebcelllymphoma |