Dynamic single-cell mapping unveils Epstein‒Barr virus-imprinted T-cell exhaustion and on-treatment response
Abstract Epstein‒Barr virus (EBV)-associated gastric cancer (GC) manifests an intriguing immunotherapy response. However, the cellular basis for EBV-imprinted tumour immunity and on-treatment response remains undefined. This study aimed to finely characterize the dynamic tumour immune contexture of human EBV (+) GC treated with immunochemotherapy by longitudinal scRNA-seq and paired scTCR/BCR-seq. EBV (+) GC exhibits an inflamed-immune phenotype with increased T-cell and B-cell infiltration. Immunochemotherapy triggers clonal revival and reinvigoration of effector T cells which step to determine treatment response. Typically, an antigen-specific ISG-15+CD8+ T-cell population is highly enriched in EBV (+) GC patients, which represents a transitory exhaustion state. Importantly, baseline intratumoural ISG-15+CD8+ T cells predict immunotherapy responsiveness among GC patients. Re-emerged clonotypes of pre-existing ISG-15+CD8+ T cells could be found after treatment, which gives rise to a CXCL13-expressing effector population in responsive EBV (+) tumours. However, LAG-3 retention may render the ISG-15+CD8+ T cells into a terminal exhaustion state in non-responsive EBV (+) tumours. In accordance, anti-LAG-3 therapy could effectively reduce tumour burden in refractory EBV (+) GC patients. Our results delineate a distinct implication of EBV-imprinted on-treatment T-cell immunity in GC, which could be leveraged to optimize the rational design of precision immunotherapy..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
Signal Transduction and Targeted Therapy - 8(2023), 1, Seite 13 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Miao-Zhen Qiu [VerfasserIn] |
|---|
| Links: |
doi.org [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1038/s41392-023-01622-1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
DOAJ091739217 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ091739217 | ||
| 003 | DE-627 | ||
| 005 | 20240412215334.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240412s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41392-023-01622-1 |2 doi | |
| 035 | |a (DE-627)DOAJ091739217 | ||
| 035 | |a (DE-599)DOAJ070815274a0c48edad394ffc82fe221e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 050 | 0 | |a QH301-705.5 | |
| 100 | 0 | |a Miao-Zhen Qiu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dynamic single-cell mapping unveils Epstein‒Barr virus-imprinted T-cell exhaustion and on-treatment response |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Epstein‒Barr virus (EBV)-associated gastric cancer (GC) manifests an intriguing immunotherapy response. However, the cellular basis for EBV-imprinted tumour immunity and on-treatment response remains undefined. This study aimed to finely characterize the dynamic tumour immune contexture of human EBV (+) GC treated with immunochemotherapy by longitudinal scRNA-seq and paired scTCR/BCR-seq. EBV (+) GC exhibits an inflamed-immune phenotype with increased T-cell and B-cell infiltration. Immunochemotherapy triggers clonal revival and reinvigoration of effector T cells which step to determine treatment response. Typically, an antigen-specific ISG-15+CD8+ T-cell population is highly enriched in EBV (+) GC patients, which represents a transitory exhaustion state. Importantly, baseline intratumoural ISG-15+CD8+ T cells predict immunotherapy responsiveness among GC patients. Re-emerged clonotypes of pre-existing ISG-15+CD8+ T cells could be found after treatment, which gives rise to a CXCL13-expressing effector population in responsive EBV (+) tumours. However, LAG-3 retention may render the ISG-15+CD8+ T cells into a terminal exhaustion state in non-responsive EBV (+) tumours. In accordance, anti-LAG-3 therapy could effectively reduce tumour burden in refractory EBV (+) GC patients. Our results delineate a distinct implication of EBV-imprinted on-treatment T-cell immunity in GC, which could be leveraged to optimize the rational design of precision immunotherapy. | ||
| 653 | 0 | |a Medicine | |
| 653 | 0 | |a R | |
| 653 | 0 | |a Biology (General) | |
| 700 | 0 | |a Chaoye Wang |e verfasserin |4 aut | |
| 700 | 0 | |a Zhiying Wu |e verfasserin |4 aut | |
| 700 | 0 | |a Qi Zhao |e verfasserin |4 aut | |
| 700 | 0 | |a Zhibin Zhao |e verfasserin |4 aut | |
| 700 | 0 | |a Chun-Yu Huang |e verfasserin |4 aut | |
| 700 | 0 | |a Wenwei Wu |e verfasserin |4 aut | |
| 700 | 0 | |a Li-Qiong Yang |e verfasserin |4 aut | |
| 700 | 0 | |a Zhi-Wei Zhou |e verfasserin |4 aut | |
| 700 | 0 | |a Yu Zheng |e verfasserin |4 aut | |
| 700 | 0 | |a Hong-Ming Pan |e verfasserin |4 aut | |
| 700 | 0 | |a Zexian Liu |e verfasserin |4 aut | |
| 700 | 0 | |a Zhao-Lei Zeng |e verfasserin |4 aut | |
| 700 | 0 | |a Hui-Yan Luo |e verfasserin |4 aut | |
| 700 | 0 | |a Feng Wang |e verfasserin |4 aut | |
| 700 | 0 | |a Feng-Hua Wang |e verfasserin |4 aut | |
| 700 | 0 | |a Si-Yu Yang |e verfasserin |4 aut | |
| 700 | 0 | |a Meng-Xing Huang |e verfasserin |4 aut | |
| 700 | 0 | |a Zhexiong Lian |e verfasserin |4 aut | |
| 700 | 0 | |a Haiyan Zhang |e verfasserin |4 aut | |
| 700 | 0 | |a Rui-Hua Xu |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t Signal Transduction and Targeted Therapy |d Nature Publishing Group, 2016 |g 8(2023), 1, Seite 13 |w (DE-627)DOAJ000142190 |x 20593635 |7 nnns |
| 773 | 1 | 8 | |g volume:8 |g year:2023 |g number:1 |g pages:13 |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41392-023-01622-1 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/070815274a0c48edad394ffc82fe221e |z kostenfrei |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41392-023-01622-1 |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/2059-3635 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 951 | |a AR | ||
| 952 | |d 8 |j 2023 |e 1 |h 13 | ||