Effects of B-Cell Lymphoma on the Immune System and Immune Recovery after Treatment: The Paradigm of Targeted Therapy

Abstract

B-cell lymphoma and lymphoproliferative diseases represent a heterogeneous and complex group of neoplasms that are accompanied by a broad range of immune regulatory disorder phenotypes. Clinical features of autoimmunity, hyperinflammation, immunodeficiency and infection can variously dominate, depending on the immune pathway most involved. Immunological imbalance can play a role in lymphomagenesis, also supporting the progression of the disease, while on the other hand, lymphoma acts on the immune system to weaken immunosurveillance and facilitate immunoevasion. Therefore, the modulation of immunity can have a profound effect on disease progression or resolution, which makes the immune system a critical target for new therapies. In the current therapeutic scenario enriched by chemo-free regimens, it is important to establish the effect of various drugs on the disease, as well as on the restoration of immune functions. In fact, treatment of B-cell lymphoma with passive immunotherapy that targets tumor cells or targets the tumor microenvironment, together with adoptive immunotherapy, is becoming more frequent. The aim of this review is to report relevant data on the evolution of the immune system during and after treatment with targeted therapy of B-cell lymphomas.

Age‐related immune cell dynamics influence outcomes after allogeneic haematopoietic cell transplantation

“…It is intriguing to note that a negative predictor of humoral responses was donor EBV serostatus, and accordingly, patients reactivating EBV showed a worse trend in B cell and IgM repertoire, regardless of previous anti‐CD20 exposure. This observation is in line with the effect of B‐cell depleting therapies shown in other disease settings 33–36 …”

“…This observation is in line with the effect of B-cell depleting therapies shown in other disease settings. [33][34][35][36] Besides the differences in age, we showed the impact of immune recovery on clinical outcomes, demonstrating a drop in survival when none of the immune subsets recovered within the first post-HCT year. The interesting aspect is that among all the lymphoid lineages, CD4+ T and B cells were those mostly impacting survival probabilities.…”

Risk factors and outcomes of Pneumocystis pneumonia in solid organ transplant recipients: Impact of posttransplant lymphoproliferative disorder

“…Lymphoma itself has been implicated in causing immune dysfunction, and it is possible that PTLD, in conjunction with underlying maintenance immunosuppression, may lead to opportunistic infection in the absence of chemotherapy. 13 Finally, multiple measures of immunosuppression have been associated with development of PTLD, and it is possible that many of the same factors that led to PTLD may have also predisposed to PJP. 5,14 Lymphopenia has been found in multiple studies to be associated with PJP.…”

Infectious complications among CD19 CAR‐T cell therapy recipients: A single‐center experience

“…2 Risk factors include the underlying hematologic malignancy, prior lines of chemotherapy, depth and duration of leukopenia, and the need for treatment of CD19 CAR-T cell therapy complications, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). [2][3][4][5][6] Treatment of CRS and ICANS requires immunosuppressive agents, including interleukin-6 blockers such as tocilizumab and high-dose corticosteroids, further contributing to risk of infection. 7 Currently, no consensus approach exists for antimicrobial prophylaxis in CD19 CAR-T cell therapy, and strategies are mostly extrapolated from autologous hematopoietic stem cell transplant (HSCT) patients.…”

“…Rates of infection in patients receiving CD19 CAR‐T cell therapy vary from 18% to 56% in prospective registrational clinical trials and from 2% to 60% in subsequent retrospective analyses 2 . Risk factors include the underlying hematologic malignancy, prior lines of chemotherapy, depth and duration of leukopenia, and the need for treatment of CD19 CAR‐T cell therapy complications, including cytokine release syndrome (CRS) and immune effector cell‐associated neurotoxicity syndrome (ICANS) 2–6 . Treatment of CRS and ICANS requires immunosuppressive agents, including interleukin‐6 blockers such as tocilizumab and high‐dose corticosteroids, further contributing to risk of infection 7 …”