Figure 2.

Lymphoma cells express MHC class I (a), surface markers of “self,” antiphagocytic (“don’t eat me,”) and phagocytic (“eat me”) signals. Engagement of CD47 (i.e., “don’t eat me” signal) on lymphoma cells with SIRPα on macrophages causes activation and phosphorylation of SIRPα ITIM motifs and the recruitment of SHP-1 phosphatases (b) preventing myosin-IIA accumulation at the phagocytic synapse, which results in inhibiting lymphoma cell phagocytosis. Blocking the CD47:SIRPα engagement with anti-CD47 antibodies (c) leads to an increase in lymphoma cell phagocytosis by APCs. In turn, the engulfed lymphoma cells are processed (d), and these APCs present lymphoma-associated antigens on their MHC (e). Then, naïve tumor reactive T cells (f) can engage with MHC on the APCs that present lymphoma neoantigens with additional costimulatory molecules (g). These lymphoma-specific T cells are thereby activated, expand, and can cause antigen-specific lymphoma cell cytotoxicity (h) on remaining lymphoma cells. TCR, T-cell receptor.