{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:31:47Z","timestamp":1786516307225,"version":"build-2736575974"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:p>\n                    Metastatic breast cancer remains difficult to cure, and the way B and T lymphocytes adapt across metastatic niches especially under therapy remains insufficiently defined. Clarifying compartment specific immune remodeling may help explain resistance to PD-1\/PD-L1 blockade and identify actionable targets. We performed an integrated meta-analysis of single cell RNA-seq datasets from normal breast tissue, primary tumors, tumor-draining lymph nodes (TLNs), and peripheral blood mononuclear cells (PBMCs), focusing on B and Tcell states. Immune composition differed notably by compartment. Tumors were enriched for effector CD8 states (CD8 cytotoxic 20.1%; CD8 activated 13.5%), whereas TLNs preserved larger na\u00efve and memory reservoirs (CD4 na\u00efve 40.7%; B na\u00efve 11.4%; B memory 12.0%) and contained a higher B cell fraction than tumors (39.6% vs. 19.5%). Post therapy, PBMCs and TLNs showed increased BTLA-HVEM (TNFRSF14) checkpoint signaling and enhanced MIF-CD74 interactions with a shift from CD44 toward CXCR4, consistent with CXCR4 driven migratory and survival programs. In TLNs, TNFRSF14 signaling was unidirectional (B\u2192T), absent in the reverse direction, and not detected in tumors. Clinically, higher tumor CXCR4 combined with lower TNFRSF14 was associated with shorter progression free survival in TCGA-BRCA, most evident in node positive, early stage disease. To target the BTLA-HVEM checkpoint axis, we performed structure guided\n                    <jats:italic>de novo<\/jats:italic>\n                    peptide design using the native HVEM (23-39) peptide as an active structural template, followed by docking and molecular dynamics simulations. The optimized De novo-P2 peptide showed stable and favorable interactions at the BTLA interface, supporting its potential as a competitive modulator of BTLA-HVEM signaling. These data define niche specific lymphocyte remodeling and implicate BTLA-HVEM and CXCL12-CXCR4 as candidate biomarkers and therapeutic targets linked to PD-1\/PD-L1 resistance.\n                  <\/jats:p>","DOI":"10.3389\/fbinf.2026.1833416","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:59:56Z","timestamp":1786514396000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Single cell mapping of B and T cell dynamics in breast cancer lymph node metastasis"],"prefix":"10.3389","volume":"6","author":[{"given":"Sajid","family":"Khan","sequence":"first","affiliation":[{"name":"Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Pharmacology, School of Basic Medical Science, Base for International Science and Technology Cooperation, Carson Cancer Stem Cell Vaccines R&D Center, International Cancer Center, Shenzhen University Medical School, Shenzhen University","place":["Shenzhen, China"]},{"name":"Department of Bioinformatics, Government Postgraduate College Mandian","place":["Abbottabad, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabahat","family":"Jamil","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Government Postgraduate College Mandian","place":["Abbottabad, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Hamza","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Government Postgraduate College Mandian","place":["Abbottabad, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarlish","family":"Attique","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Government Postgraduate College Mandian","place":["Abbottabad, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Pharmacology, School of Basic Medical Science, Base for International Science and Technology Cooperation, Carson Cancer Stem Cell Vaccines R&D Center, International Cancer Center, Shenzhen University Medical School, Shenzhen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"673051","DOI":"10.3389\/fmolb.2021.673051","article-title":"Immune crosstalk between lymph nodes and breast carcinomas, with a focus on B cells","volume":"8","author":"Alberts","year":"2021","journal-title":"Front. 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