CD19-directed chimeric antigen receptor T cell therapy (CART19) is a standard second- or third-line treatment for relapsed/refractory large B-cell lymphoma (LBCL), yet only 30% of patients (pts) achieve durable remission. We analyzed 15 LBCL pts treated with CART19, including 8 complete responders (CR ≥1 year) and 7 with progressive disease (PD). We generated a longitudinal single-cell CITE-seq and TCR-seq atlas of 67 peripheral blood samples with 65,427 CAR+ and 298,838 CAR- cells across apheresis (APH), infusion product, baseline, peak, and week 4. CD4+ T cells are enriched in the product, yet CR pts saw expansion of CD8+ effector memory (EM) CAR T cells post-infusion. TCR profiling revealed no significant CAR+ clonal selection. Gene set enrichment analysis showed opposing immune signaling pathways in CD8+ EM CAR T cells, with tumor necrosis factor alpha (TNFa) via NFkB signaling enriched in CR and interferon (IFN) response in PD pts. Conversely at APH, TNFa signaling was upregulated in PD pts. We saw parallel signaling patterns in myeloid cells. PD showed persistent IFN gene signatures, while dendritic cells in CR showed elevated TNFa signaling. Cell-cell communication analysis showed these pathways shape intracellular crosstalk. Increased TNFa ligand signaling in PD at APH was observed, shifting to TNF family ligands (LTA, LTB) in CR later. PD also exhibited sustained type I/II IFN signaling across time and elevated IFN gamma expression at APH. Together, these data suggest synergistic TNF and IFN gamma signaling in APH in PD leads to chronic IFN-driven signaling post-infusion promoting CART dysfunction, while acute TNF family signaling in CR supports durable response.