TY - JOUR
T1 - Follicular lymphoma and macrophages
T2 - Impact of approved and novel therapies
AU - Gouni, Sushanth
AU - Marques-Piubelli, Mario L.
AU - Strati, Paolo
N1 - Publisher Copyright:
© 2021 by The American Society of Hematology.
PY - 2021/10/26
Y1 - 2021/10/26
N2 - The survival and proliferation of follicular lymphoma (FL) cells are strongly dependent on macrophages, because their presence is necessary for the propagation of FL cells in vitro. To this regard, as also shown for the majority of solid tumors, a high tissue content of tumor-associated macrophages (TAMs), particularly if showing a protumoral phenotype (also called M2), is strongly associated with a poor outcome among patients with FL treated with chemotherapy. The introduction of rituximab, an anti-CD20 antibody that can be used by TAMs to facilitate antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis, has challenged this paradigm. In the rituximab era, clinical studies have yielded conflicting results in FL, showing variable outcomes based on the type of regimen used. This highlighted, for the first time, that the impact of TAMs on the prognosis of patients with FL may depend on the administered treatment, emphasizing the need to better understand how currently available therapies affect macrophage function in FL. We summarize the impact of approved and novel therapies for FL, including radiation therapy, chemotherapy, anti-CD20 monoclonal antibodies, lenalidomide, and targeted agents, on the biology of TAMs and describe their effects on macrophage phagocytosis, polarization, and function. Although novel agents targeting the CD47/SIRPa axis are being developed and show promising activity in FL, a deeper understanding of macrophage biology and their complex pathways will help to develop novel and safer therapeutic strategies for patients with this type of lymphoma.
AB - The survival and proliferation of follicular lymphoma (FL) cells are strongly dependent on macrophages, because their presence is necessary for the propagation of FL cells in vitro. To this regard, as also shown for the majority of solid tumors, a high tissue content of tumor-associated macrophages (TAMs), particularly if showing a protumoral phenotype (also called M2), is strongly associated with a poor outcome among patients with FL treated with chemotherapy. The introduction of rituximab, an anti-CD20 antibody that can be used by TAMs to facilitate antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis, has challenged this paradigm. In the rituximab era, clinical studies have yielded conflicting results in FL, showing variable outcomes based on the type of regimen used. This highlighted, for the first time, that the impact of TAMs on the prognosis of patients with FL may depend on the administered treatment, emphasizing the need to better understand how currently available therapies affect macrophage function in FL. We summarize the impact of approved and novel therapies for FL, including radiation therapy, chemotherapy, anti-CD20 monoclonal antibodies, lenalidomide, and targeted agents, on the biology of TAMs and describe their effects on macrophage phagocytosis, polarization, and function. Although novel agents targeting the CD47/SIRPa axis are being developed and show promising activity in FL, a deeper understanding of macrophage biology and their complex pathways will help to develop novel and safer therapeutic strategies for patients with this type of lymphoma.
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U2 - 10.1182/bloodadvances.2021005722
DO - 10.1182/bloodadvances.2021005722
M3 - Review article
C2 - 34570196
AN - SCOPUS:85118558593
SN - 2473-9529
VL - 5
SP - 4303
EP - 4312
JO - Blood Advances
JF - Blood Advances
IS - 20
ER -