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However, the comprehensive spatial pharmacodynamics of TLSs are largely unclear. In this study, we performed multifaceted spatial transcriptomic analysis with whole-transcriptome coverage and single-cell resolution, complemented by high-throughput spatial proteomics, to thoroughly characterize TLSs in clinical breast cancer samples after neoadjuvant therapy (NAT). Notably, spatial multiomic data identified that precursors of exhausted T (Tpex) cells preferentially reside within TLSs. Spatial transcriptomics with T-cell receptor repertoire sequencing revealed the presence of tumor-specific Tpex cells inside TLSs and their clonally related terminally differentiated effector T cells outside TLSs. B cells are nearest neighbors of Tpex cells in TLSs and promote invigoration of Tpex cells via ICOSL\u2013ICOS and CD86\u2013CD28 interactions within TLSs. These findings extend the current understanding of TLS spatial architecture and highlight a therapy-induced evolution of antitumor immune responses driven by the interaction between Tpex cells and B cells within TLSs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>We provide a comprehensive spatial multiomic atlas of TLSs and identify invigoration of Tpex cells by B cells in this immunologic niche as a key driver of neoadjuvant therapy\u2212induced evolution of antitumor immune responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-25-0806","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T13:25:53Z","timestamp":1782307553000},"page":"OF1-OF28","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial Multiomics Implicates the Interaction 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