Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis

Nat Commun. 2019 Feb 1;10(1):533. doi: 10.1038/s41467-018-08013-z.

Abstract

CD47 is a prominent new target in cancer immunotherapy, with antagonistic antibodies currently being evaluated in clinical trials. For effective evaluation of this strategy it is crucial to identify which patients are suited for CD47-targeted therapy. In this respect, expression of the pro-phagocytic signal SLAMF7 on both macrophages and cancer cells was recently reported to be a requisite for CD47 antibody-mediated phagocytosis. Here, we demonstrate that in fact SLAMF7 expression on cancer cells is not required and does not impact on CD47 antibody therapy. Moreover, SLAMF7 also does not impact on phagocytosis induction by CD20 antibody rituximab nor associates with overall survival of Diffuse Large B-Cell Lymphoma patients. In contrast, expression of CD47 negatively impacts on overall and progression free survival. In conclusion, cancer cell expression of SLAMF7 is not required for phagocytosis and, in contrast to CD47 expression, should not be used as selection criterion for CD47-targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • CD47 Antigen / metabolism*
  • Cell Line, Tumor
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Macrophages / metabolism
  • Phagocytosis*
  • Prednisone / therapeutic use
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rituximab
  • Signaling Lymphocytic Activation Molecule Family / genetics
  • Signaling Lymphocytic Activation Molecule Family / metabolism*
  • Survival Analysis
  • Vincristine / therapeutic use

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • CD47 Antigen
  • CD47 protein, human
  • R-CHOP protocol
  • RNA, Messenger
  • SLAMF7 protein, human
  • Signaling Lymphocytic Activation Molecule Family
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone