Impact of MYC on Anti-Tumor Immune Responses in Aggressive B Cell Non-Hodgkin Lymphomas: Consequences for Cancer Immunotherapy

SIMPLE SUMMARY: The human immune system has several mechanisms to attack and eliminate lymphomas. However, the MYC oncogene is thought to facilitate escape from this anti-tumor immune response. Since patients with MYC overexpressing lymphomas face a significant dismal prognosis after treatment with standard immunochemotherapy, understanding the role of MYC in regulating the anti-tumor immune response is highly relevant. In this review, we describe the mechanisms by which MYC attenuates the anti-tumor immune responses in B cell non-Hodgkin lymphomas. We aim to implement this knowledge in the deployment of novel immunotherapeutic approaches. Therefore, we also provide a comprehensive overview of current immunotherapeutic options and we discuss potential future treatment strategies for MYC overexpressing lymphomas. ABSTRACT: Patients with MYC overexpressing high grade B cell lymphoma (HGBL) face significant dismal prognosis after treatment with standard immunochemotherapy regimens. Recent preclinical studies indicate that MYC not only contributes to tumorigenesis by its effects on cell proliferation and differentiation, but also plays an important role in promoting escape from anti-tumor immune responses. This is of specific interest, since reversing tumor immune inhibition with immunotherapy has shown promising results in the treatment of both solid tumors and hematological malignancies. In this review, we outline the current understanding of impaired immune responses in B cell lymphoid malignancies with MYC overexpression, with a particular emphasis on diffuse large B cell lymphoma. We also discuss clinical consequences of MYC overexpression in the treatment of HGBL with novel immunotherapeutic agents and potential future treatment strategies.