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

Mol Cancer. 2024 Sep 28;23(1):210. doi: 10.1186/s12943-024-02123-7.

Abstract

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.

Keywords: CD16+ T cell; CD16+ monocyte; aggressive B-NHL (non-Hodgkin B cell lymphoma); antibody-dependent cellular cytotoxicity (ADCC); diffuse large B cell lymphoma (DLBCL); rituximab.

Publication types

  • Letter

MeSH terms

  • Aged
  • Antibody-Dependent Cell Cytotoxicity
  • Biomarkers, Tumor
  • Female
  • GPI-Linked Proteins / blood
  • GPI-Linked Proteins / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • 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
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Receptors, IgG* / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Receptors, IgG
  • FCGR3B protein, human
  • Biomarkers, Tumor
  • GPI-Linked Proteins