{
  "abstract": "Background: Relapsed/refractory multiple myeloma (RR-MM) remains a major therapeutic challenge despite the efficacy of BCMA-directed CAR-T therapy. However, mechanisms of innate immune reconstitution remain poorly understood. Monocytes regulate antigen presentation, inflammation, and immune homeostasis, with HLA-DR reflecting their functional state. Characterizing monocyte phenotypes may provide insights into post-CAR-T immune recovery. Aim: To characterize monocyte phenotypic remodeling during immune reconstitution following BCMA CAR-T cell therapy and identify distinct immune states associated with impaired antigen-presenting profiles during immune reconstitution. Methodology: Patients with RR-MM treated with BCMA-directed CAR-T cells were prospectively enrolled. Peripheral blood samples were collected immediately before infusion (baseline) and 30 days post-infusion (D+30). Peripheral blood mononuclear cells were analyzed by multiparametric flow cytometry using CD45, CD14, CD16, HLA-DR, CD80, CD86, CD11b, CD11c, CD62L, CD19, and CD56. Monocyte subsets were defined according to CD14/CD16 expression and further characterized based on markers associated with antigen presentation, activation, co-stimulation, and migration. Changes in monocyte subset frequency and phenotype, including CD14⁺HLA-DR^low/- populations, were evaluated between baseline and D+30. Results: Paired analysis of three patients demonstrated heterogeneous monocyte reconstitution after BCMA-directed CAR-T therapy. The patient with the highest circulating CAR-T cell frequency exhibited the most pronounced remodeling, with reduced total CD14⁺ and classical monocytes and relative expansion of non-classical monocytes. Across patients, classical monocytes shifted toward an HLA-DR-intermediate phenotype, while HLA-DR-negative intermediate monocytes consistently decreased. In patients with low baseline HLA-DR expression, this was accompanied by increased HLA-DR fluorescence intensity, suggesting partial restoration of antigen-presenting capacity. Co-stimulatory remodeling was subset-specific: HLA-DR⁺ intermediate monocytes showed increased CD80⁺CD86⁻ cells, whereas HLA-DR⁺ non-classical monocytes displayed increased CD80⁻CD86⁺ cells. Residual HLA-DR⁻ non-classical monocytes remained enriched for a CD80⁻CD86⁻ phenotype. Classical and intermediate monocytes were predominantly CD11b⁺CD11c⁺, while non-classical monocytes exhibited greater CD11b/CD11c heterogeneity. Discussion: These findings suggest that early immune reconstitution following BCMA-directed CAR-T therapy is characterized by heterogeneous rather than uniform monocyte recovery. The reduction of HLA-DR-negative intermediate monocytes may indicate partial restoration of antigen presentation, whereas persistence of HLA-DR⁻CD80⁻CD86⁻ non-classical monocytes suggest incomplete recovery of co-stimulatory function. CD11b/CD11c heterogeneity further supports the existence of distinct activation and migratory states within the monocyte compartment. Conclusion: Early immune reconstitution after BCMA-directed CAR-T therapy is associated with dynamic remodeling of monocyte subsets and partial recovery of antigen-presenting phenotypes. Persistent HLA-DR⁻ non-classical monocytes may represent a distinct immune state associated with incomplete innate immune recovery. These findings support further investigation of monocyte functional states as biomarkers of immune reconstitution following CAR-T therapy.",
  "abstract_shown": true,
  "affiliations": [
    "A.C.Camargo Cancer Center, São Paulo, SP, Brasil",
    "Universidade Federal de Juiz de Fora, Minas Gerais, MG, Brasil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Raquel GARCIA DA SILVA"
    },
    {
      "affs": [
        0
      ],
      "name": "Arianne FAGOTTI GUSMÃO"
    },
    {
      "affs": [
        0
      ],
      "name": "Vanessa DOS ANJOS BOVOLENTA"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniela DELECHIAVE"
    },
    {
      "affs": [
        0
      ],
      "name": "Gabriel ANDRADE DE PAULA"
    },
    {
      "affs": [
        0
      ],
      "name": "Mariana SOARES GOMES"
    },
    {
      "affs": [
        0
      ],
      "name": "Ana Luiza SIONTI PACHECO"
    },
    {
      "affs": [
        0
      ],
      "name": "Larissa CAMPOS DE SOUZA"
    },
    {
      "affs": [
        0
      ],
      "name": "Filipe FREIRES DOS SANTOS"
    },
    {
      "affs": [
        0
      ],
      "name": "Ana COSTA CORDEIRO"
    },
    {
      "affs": [
        1
      ],
      "name": "Alexandre SILVA CHAVES"
    },
    {
      "affs": [
        0
      ],
      "name": "Marta Maria MOREIRA LEMOS"
    },
    {
      "affs": [
        0
      ],
      "name": "Marina DE MATTOS NASCIMENTO"
    },
    {
      "affs": [
        0
      ],
      "name": "Lais Lie SENDA DE ABRANTES"
    },
    {
      "affs": [
        0
      ],
      "name": "Sabrina PINHO COSTA MENDES"
    },
    {
      "affs": [
        0
      ],
      "name": "Mariela PIRES CABRAL PICCIN"
    },
    {
      "affs": [
        0
      ],
      "name": "Jayr SCHMIDIT FILHO"
    },
    {
      "affs": [
        0
      ],
      "name": "Marjorie VIEIRA BATISTA"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5q3y660h2vd2y.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.107862",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926016093",
  "id": "5q3y660h2vd2y",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.107862",
  "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",
      "2720|Multiple Myeloma Research and Treatments"
    ]
  ],
  "openalex": "W7223152425",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/5q3y660h2vd2y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:26Z",
      "native_id": "7b3b003bdbd74fc09dc43e9408b8346f",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.107862"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC633-647.5",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "DISTINCT MONOCYTE STATES EMERGE DURING IMMUNE RECONSTITUTION AFTER BCMA CAR-T THERAPY IN RELAPSED/REFRACTORY MULTIPLE MYELOMA",
  "title_text": "DISTINCT MONOCYTE STATES EMERGE DURING IMMUNE RECONSTITUTION AFTER BCMA CAR-T THERAPY IN RELAPSED/REFRACTORY MULTIPLE MYELOMA",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:26Z",
  "url": "https://research.draconitic.com/paper/5q3y660h2vd2y",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}