Models of systemic immunity before and after lymphoma diagnosis. Depictions of the systemic immune state in patients who attain durable CR (models A-C) or patients with multiple relapses (model D). The lightning symbol indicates lymphoma diagnosis or relapse. In models A and B, patients have normal systemic immunity until the tumor diagnosis, at which point systemic immune dysregulation is caused by the tumor. Model A, where tumor response results in reversion to normal systemic immunity over time, is not supported by the data of Pelzl et al. In model B, tumor-driven dysregulation of systemic immunity leaves a long-lasting imprint. In model C, systemic immune dysregulation precedes lymphomagenesis, and tumor clearance has minimal effects on this chronic process. Model D depicts progressive worsening of the systemic dysregulation associated with multiple relapses and treatment. Figure created with Biorender.com.