{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T23:15:17Z","timestamp":1790118917641,"version":"4.0.1"},"reference-count":20,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["Nos. 82293632, 82293630 and 82070152"],"award-info":[{"award-number":["Nos. 82293632, 82293630 and 82070152"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["No. 21623121"],"award-info":[{"award-number":["No. 21623121"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Immunopathol Pharmacol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>\n                    This study aims to identify differentially upregulated ligand-receptor interactions between B-ALL cells and exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and to develop a multivariate Cox regression model for predicting the overall survival of pediatric B-ALL patients based on CCL3\/CCL4\/CCL5 expression levels. Pediatric B cell-acute lymphoblastic leukemia (B-ALL) is a hematopoietic malignancy. T cell exhaustion has an important impact on the prognosis of leukemia. The interaction between tumor cells and T cells can influence the degree of T cell exhaustion. However, the effects of B-ALL cells on exhausted T cell subpopulations and how the interaction influences the prognosis of B-ALL patients remain unclear. Single-cell RNA sequencing (scRNA-Seq) data from pediatric B-ALL patients were downloaded from GEO. Cell interaction analysis identified ligand-receptor pairs between B-ALL cells and exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell. To confirm the function of\n                    <jats:italic toggle=\"yes\">CCL3<\/jats:italic>\n                    \/\n                    <jats:italic toggle=\"yes\">CCL4<\/jats:italic>\n                    \/\n                    <jats:italic toggle=\"yes\">CCL5<\/jats:italic>\n                    \/\n                    <jats:italic toggle=\"yes\">CCR5<\/jats:italic>\n                    in prognosis prediction, quantitative real-time polymerase chain reaction (qRT-PCR) was employed. We further developed an innovative stratified model that integrates\n                    <jats:italic toggle=\"yes\">CCL3<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">CCL4<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">CCL5<\/jats:italic>\n                    through multi-Cox regression. Clustering of scRNA-Seq data revealed an increased proportion of exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in relapsed B-ALL, especially terminal exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells (CD8_Ex), with increased exhaustion and decreased proliferation scores. Moreover, the CCL3\/CCL4\/CCL5-CCR5 axis was upregulated in interactions between B-ALL cells and terminal CD8_Ex. Transcriptome data from 221 pediatric B-ALL samples revealed that high CCL3\/CCL4\/CCL5\/CCR5 levels correlate with low overall survival (OS). A multivariate Cox regression model incorporating CCL3\/CCL4\/CCL5 predicted prognoses. Finally, a model based on the adult B-ALL patients from our center also accurately predicted prognoses. We report for the first time the crucial role of the CCL3\/CCL4\/CCL5-CCR5 axis in the differentiation of terminal exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in B-ALL. High expression of CCL3, CCL4, CCL5, and CCR5 correlates with poor prognosis in B-ALL, suggesting potential biomarkers and therapeutic targets.\n                  <\/jats:p>","DOI":"10.1177\/03946320251346823","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T03:05:34Z","timestamp":1750820734000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["High expression of CCL3\/CCL4\/CCL5\/CCR5 promotes exhausted CD8\n                    <sup>+<\/sup>\n                    T cells terminal differentiation and is associated with poor prognosis in pediatric B-ALL patients"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7894-7564","authenticated-orcid":false,"given":"Jiamian","family":"Zheng","sequence":"first","affiliation":[{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China"},{"name":"Department of Hematology, First Af\ufb01liated Hospital, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China"},{"name":"Department of Hematology, First Af\ufb01liated Hospital, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueting","family":"Peng","sequence":"additional","affiliation":[{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cunte","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Guangzhou First People\u2019s Hospital, Institute of Blood Transfusion and Hematology, Guangzhou Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology, First Af\ufb01liated Hospital, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liye","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Hematology, First Af\ufb01liated Hospital, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0974-4036","authenticated-orcid":false,"given":"Yangqiu","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China"},{"name":"Department of Hematology, First Af\ufb01liated Hospital, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2824-187X","authenticated-orcid":false,"given":"Songnan","family":"Sui","sequence":"additional","affiliation":[{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China"},{"name":"Department of Hematology, First Af\ufb01liated Hospital, Jinan University, Guangzhou, China"},{"name":"Central People\u2019s Hospital of Zhanjiang, Zhanjiang, China"},{"name":"Zhanjiang Key Laboratory of Leukemia Pathogenesis and Targeted Therapy Research, Zhanjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05690"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-024-00593-5"},{"key":"e_1_3_3_4_2","article-title":"Single-cell RNA-Seq of T cells in B-ALL patients reveals an exhausted subset with remarkable heterogeneity","volume":"8","author":"Wang X","year":"2021","unstructured":"Wang X, Chen Y, Li Z, et al. (2021) Single-cell RNA-Seq of T cells in B-ALL patients reveals an exhausted subset with remarkable heterogeneity. 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