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Tumor-specific CD4+ T cells eradicate myeloma cells genetically deficient in MHC class II display

2016; Impact Journals LLC; Volume: 7; Issue: 41 Linguagem: Inglês

10.18632/oncotarget.11946

1949-2553

Anders Tveita, Marte Fauskanger, Bjarne Bogen, Ole Audun Werner Haabeth,

Immune Cell Function and Interaction

// Anders Tveita 1 , Marte Fauskanger 1 , Bjarne Bogen 1, 2 , Ole Audun Werner Haabeth 1 1 Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway 2 KG Jebsen Centre for Research on Influenza Vaccines, Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway Correspondence to: Ole Audun Werner Haabeth, email: o.a.haabeth@medisin.uio.no Bjarne Bogen, email: bjarne.bogen@medisin.uio.no Keywords: CD4+ T cells, MHC class II, tumor immunology, antigen presentation, anti-tumor immunity Received: May 06, 2016 Accepted: September 02, 2016 Published: September 10, 2016 ABSTRACT CD4 + T cells have been shown to reject tumor cells with no detectable expression of major histocompatibility complex class II (MHC II). However, under certain circumstances, induction of ectopic MHC II expression on tumor cells has been reported. To confirm that CD4 + T cell-mediated anti-tumor immunity can be successful in the complete absence of antigen display on the tumor cells themselves, we eliminated MHC II on tumor cells using CRISPR/Cas9. Our results demonstrate that ablation of the relevant MHC II (I-E d ) in multiple myeloma cells (MOPC315) does not hinder rejection by tumor-specific CD4 + T cells. These findings provide conclusive evidence that CD4 + T cells specific for tumor antigens can eliminate malignant cells in the absence of endogenous MHC class II expression on the tumor cells. This occurs through antigen uptake and indirect presentation on tumor-infiltrating macrophages.