CD16+ as predictive marker for early relapse in aggressive B-NHL/DLBCL patients

Assessing the prognosis of patients with aggressive non-Hodgkin B cell lymphoma mainly relies on a clinical risk score (IPI). Standard first-line therapies are based on a chemo-immunotherapy with rituximab, which mediates CD16-dependent antibody-dependent cellular cytotoxicity (ADCC). We phenotypica...

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Published in:	Molecular cancer Vol. 23; no. 1; pp. 210 - 9
Main Authors:	Zöphel, Sylvia, Küchler, Nadja, Jansky, Johanna, Hoxha, Cora, Schäfer, Gertrud, Weise, Julius J, Vialle, Joanne, Kaschek, Lea, Stopper, Gebhard, Eichler, Hermann, Yildiz, Daniela, Moter, Alina, Wendel, Philipp, Ullrich, Evelyn, Schormann, Claudia, Rixecker, Torben, Cetin, Onur, Neumann, Frank, Orth, Patrick, Bewarder, Moritz, Hoth, Markus, Thurner, Lorenz, Schwarz, Eva C
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 28-09-2024 BioMed Central BMC
Subjects:	Aged aggressive B-NHL (non-Hodgkin B cell lymphoma) Antibodies Antibody-Dependent Cell Cytotoxicity antibody-dependent cellular cytotoxicity (ADCC) Biomarkers, Tumor Blood Cancer CD16+ monocyte CD16+ T cell Chemotherapy Correspondence diffuse large B cell lymphoma (DLBCL) Female GPI-Linked Proteins - blood GPI-Linked Proteins - metabolism Humans Immunotherapy Kaplan-Meier Estimate Killer cells Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Lymphoma, B-Cell - blood Lymphoma, B-Cell - immunology Lymphoma, B-Cell - metabolism Lymphoma, B-Cell - pathology Male Medical examination Medical research Medicine, Experimental Middle Aged Monocytes - immunology Monocytes - metabolism Neoplasm Recurrence, Local - pathology Non-Hodgkin's lymphomas Prognosis Receptors, IgG - metabolism rituximab T cells T-Lymphocytes - immunology T-Lymphocytes - metabolism Vincristine Viral antibodies diffuse large B cell lymphoma (DLBCL) CD16+ monocyte antibody-dependent cellular cytotoxicity (ADCC) aggressive B-NHL (non-Hodgkin B cell lymphoma) rituximab CD16+ T cell
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Summary:	Assessing the prognosis of patients with aggressive non-Hodgkin B cell lymphoma mainly relies on a clinical risk score (IPI). Standard first-line therapies are based on a chemo-immunotherapy with rituximab, which mediates CD16-dependent antibody-dependent cellular cytotoxicity (ADCC). We phenotypically and functionally analyzed blood samples from 46 patients focusing on CD16+ NK cells, CD16+ T cells and CD16+ monocytes. Kaplan-Meier survival curves show a superior progression-free survival (PFS) for patients having more than 1.6% CD16+ T cells (p = 0.02; HR = 0.13 (0.007-0.67)) but an inferior PFS having more than 10.0% CD16+ monocytes (p = 0.0003; HR = 16.0 (3.1-291.9)) at diagnosis. Surprisingly, no correlation with NK cells was found. The increased risk of relapse in the presence of > 10.0% CD16+ monocytes is reversed by the simultaneous occurrence of > 1.6% CD16+ T cells. The unexpectedly strong protective function of CD16+ T cells could be explained by their high antibody-dependent cellular cytotoxicity as quantified by real-time killing assays and single-cell imaging. The combined analysis of CD16+ monocytes (> 10%) and CD16+ T cells (< 1.6%) provided a strong model with a Harrell's C index of 0.80 and a very strong power of 0.996 even with our sample size of 46 patients. CD16 assessment in the initial blood analysis is thus a precise marker for early relapse prediction.
Bibliography:	content type line 23 SourceType-Scholarly Journals-1 ObjectType-Correspondence-1
ISSN:	1476-4598 1476-4598
DOI:	10.1186/s12943-024-02123-7