CD4 and neoplasm: Mechanistically, we demonstrated that direct tumor recognition by this latter subset (tumor-recognizing CD4+ T cells: TR-CD4) requires non-classical MHC class II (MHC-II) antigen-processing pathways such as proteasomal degradation and transporter-associated with antigen-processing mediated peptide transport, that are typically involved in the MHC class I (MHC-I) presentation, and endosomal recycling.