{
  "abstract": "Background: BCMA-directed CAR-T therapy has improved outcomes in relapsed/refractory multiple myeloma (RR-MM). However, responses remain heterogeneou, suggesting that immune recovery extends beyond CAR-T expansion alone. Although most studies focus on the infused cellular product, remodeling of CAR-positive T cells, endogenous CAR-negative T cells, and natural killer (NK) cells during early immune reconstitution remains poorly understood. Aim: To characterize early lymphoid immune remodeling after BCMA-directed CAR-T therapy by integrating CAR-positive and CAR-negative T-cell compartments, CD4/CD8 balance, memory differentiation, immune checkpoints, and NK-cell subsets. Methodology: Patients with RR-MM treated with BCMA-directed CAR-T cells were prospectively enrolled (CAAE: 65750722.3.0000.5432). Blood samples were collected before infusion and 30 days after treatment. PBMC were analyzed by multiparametric flow cytometry to assess CAR-positive and CAR-negative CD4⁺ and CD8⁺ T-cell subsets, memory differentiation, checkpoint expression, and conventional and non-conventional NK-cell phenotypes. Paired changes between baseline and day 30 were evaluated. Results: Paired analyses of three patients revealed marked interindividual heterogeneity in early lymphoid reconstitution. Circulating CAR-T frequencies ranged from robust expansion to minimal detectable expansion at D30. Total CD4⁺ and CD8⁺ T-cell compartments followed distinct trajectories, producing divergent CD4/CD8 architectures. The responding patient exhibited a more balanced CD4/CD8 ratio, whereas the two non-responders developed CD4- or CD8-dominant profiles. Corresponding alterations in CD4/CD8 balance were also observed within the CAR-negative compartment, indicating that remodeling extended beyond the infused product. Effector-memory enrichment was observed across CAR-positive and CAR-negative T-cell compartments, accompanied by sustained PD-1 and reduced LAG-3 expression, particularly among CD8⁺ T cells. All patients also showed expansion of non-conventional NK cells, with relative contraction of canonical NK subsets and reduced LAG-3 expression. These findings demonstrate multi-compartment lymphoid remodeling during early immune reconstitution. Discussion: The concomitant changes observed in CAR-positive T cells, endogenous CAR-negative T cells, and NK cells suggest that early immune recovery after BCMA-directed CAR-T therapy reflects systemic lymphoid reorganization rather than expansion of the infused product alone. The expansion of non-conventional NK phenotypes across patients with markedly different CAR-T frequencies may represent a shared feature of post-lymphodepletion immune recovery. The observation that the responding patient maintained a more balanced CD4/CD8 architecture, whereas non-responders developed opposite forms of imbalance, is hypothesis-generating and suggests that the organization of immune reconstitution may be biologically relevant. However, the limited cohort precludes conclusions regarding association with clinical response. Conclusion: BCMA-directed CAR-T therapy was followed by distinct patterns of early lymphoid reconstitution involving CAR-positive T cells, endogenous CAR-negative T cells, and non-conventional NK cells. These findings support further investigation of integrated lymphoid architecture, including CD4/CD8 balance, as a potential marker of immune recovery and treatment outcome in larger longitudinal cohorts.",
  "abstract_shown": true,
  "affiliations": [
    "A.C.Camargo Cancer Center, São Paulo, SP, Brasil",
    "A.C.Camargo, São Paulo, SP, Brasil",
    "Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brasil",
    "A.C.Camargo, São Paulo, SP, Brasil; Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brasil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Arianne Fagotti GUSMAO"
    },
    {
      "affs": [
        1
      ],
      "name": "Raquel Garcia DA SILVA"
    },
    {
      "affs": [
        1
      ],
      "name": "Vanessa Dos Anjos BOVOLENTA"
    },
    {
      "affs": [
        1
      ],
      "name": "Bianca Batista CAL"
    },
    {
      "affs": [
        1
      ],
      "name": "Ana Costa CORDEIRO"
    },
    {
      "affs": [
        1
      ],
      "name": "Daniela DELECHIAVE"
    },
    {
      "affs": [
        1
      ],
      "name": "Sabrina Pinho Costa MENDES"
    },
    {
      "affs": [
        1
      ],
      "name": "Lais Lie Senda DE ABRANTES"
    },
    {
      "affs": [
        2
      ],
      "name": "Alexandre Silva CHAVES"
    },
    {
      "affs": [
        1
      ],
      "name": "Ana Luiza Sionti PACHECO"
    },
    {
      "affs": [
        1
      ],
      "name": "Larissa Souza CAMPOS"
    },
    {
      "affs": [
        1
      ],
      "name": "Mariana Soares GOMES"
    },
    {
      "affs": [
        1
      ],
      "name": "Gabriel Andrade DE PAULA"
    },
    {
      "affs": [
        1
      ],
      "name": "Filipe Freires DOS SANTOS"
    },
    {
      "affs": [
        1
      ],
      "name": "Marina De Matos NASCIMENTO"
    },
    {
      "affs": [
        1
      ],
      "name": "Mariela Pires Cabral PICCIN"
    },
    {
      "affs": [
        1
      ],
      "name": "Marta Maria Moreira LEMOS"
    },
    {
      "affs": [
        1
      ],
      "name": "Jayr Schmidt FILHO"
    },
    {
      "affs": [
        2
      ],
      "name": "Martin BONAMINO"
    },
    {
      "affs": [
        3
      ],
      "name": "Marjorie Vieira BATISTA"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ecpznqs4055tn.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.107863",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S253113792601610X",
  "id": "ecpznqs4055tn",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.107863",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7223110270",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/ecpznqs4055tn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:20Z",
      "native_id": "063a3ed86f4b4f4898f1edfce4997be2",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.107863"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "DISTINCT PATTERNS OF LYMPHOID IMMUNE RECONSTITUTION AFTER BCMA-DIRECTED CAR-T THERAPY IN RELAPSED/REFRACTORY MULTIPLE MYELOMA",
  "title_text": "DISTINCT PATTERNS OF LYMPHOID IMMUNE RECONSTITUTION AFTER BCMA-DIRECTED CAR-T THERAPY IN RELAPSED/REFRACTORY MULTIPLE MYELOMA",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:18Z",
  "url": "https://research.draconitic.com/paper/ecpznqs4055tn",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}