Linking Immunoevasion and Metabolic Reprogramming in B-Cell–Derived Lymphomas

Lymphomas represent a diverse group of malignancies that emerge from lymphocytes. Despite improvements in diagnosis and treatment of lymphomas of B-cell origin, relapsed and refractory disease represents an unmet clinical need. Therefore, it is of utmost importance to better understand the lymphomas’ intrinsic features as well as the interactions with their cellular microenvironment for developing novel therapeutic strategies. In fact, the role of immune-based approaches is steadily increasing and involves amongst others the use of monoclonal antibodies against tumor antigens, inhibitors of immunological checkpoints, and even genetically modified T-cells. Metabolic reprogramming and immune escape both represent well established cancer hallmarks. Tumor metabolism as introduced by Otto Warburg in the early 20th century promotes survival, proliferation, and therapeutic resistance. Simultaneously, malignant cells employ a plethora of mechanisms to evade immune surveillance. Increasing evidence suggests that metabolic reprogramming does not only confer cell intrinsic growth and survival advantages to tumor cells but also impacts local as well as systemic anti-tumor immunity. Tumor and immune cells compete over nutrients such as carbohydrates or amino acids that are critical for the immune cell function. Moreover, skewed metabolic pathways in malignant cells can result in abundant production and release of bioactive metabolites such as lactic acid, kynurenine or reactive oxygen species (ROS) that affect immune cell fitness and function. This “metabolic re-modeling” of the tumor microenvironment shifts anti-tumor immune reactivity toward tolerance. Here, we will review molecular events leading to metabolic alterations in B-cell lymphomas and their impact on anti-tumor immunity.