Vulnerabilities in the tumor and microenvironment in follicular lymphoma

Abstract

Follicular lymphoma (FL) is a paradigm of tumors that require the interaction between tumor and microenvironment cells to foster their development from initial steps to progression. Recent large‐scale genome studies have uncovered multiple genetic alterations of FL that influence the microenvironment in two main directions, promoting tumor cell survival and proliferation and facilitating their evasion from immune antitumor signals. Understanding the crosstalk between tumor B‐cells and the microenvironment will facilitate the identification of vulnerabilities that may offer novel targets for treatment of the patients. This review highlights recent findings showing the effect of common genetic mutations modulating the cell composition of the tumor microenvironment and the novel therapeutic perspectives to target these interactions.

Analyzing the risk factors for disease progression within 2 years and histological transformation in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone as first‐line treatment: A 15‐year follow‐up of patients with advanced follicular lymphoma in JCOG0203

“…However, our study implicated higher FLIPI scores as a risk factor, suggesting that a combination of more than one of the following risk factors comprising tumor and host factors are required to predict POD24 rather than one independent factor: age, LDH level, anemia, involved lymph node areas, and CS IV. The currently available approaches targeting the microenvironment of FL, [52][53][54][55][56][57][58][59] for instance, immunomodulatory drugs, such as lenalidomide, [60][61][62][63][64] or T-cell manipulating armaments, including chimeric antigen receptor T-cell therapies 65,66 and bispecific antibodies, [67][68][69][70][71] may reduce the incidence of POD24 and HT in the future, by altering the host immune cells surrounding FL. [72][73][74] Herein, the proportion of patients with FL with POD24 was higher than that reported in previous studies.…”

Glucose metabolism in B cell malignancies: a focus on glycolysis branching pathways

“…In B cell malignancies, the role of the TME is currently a matter of investigation. Although it is clear that bone marrow and secondary lymphoid tissues are altered [ 17 , 18 , 106 , 107 , 108 , 109 ], the specific function and contribution of each cell type to tumor progression is not completely understood yet. A common trait in B cell malignancies is the immunosuppressive component of the TME that consists of elevated numbers of exhausted T cells, regulatory T cells (Treg) and anti‐inflammatory macrophages with M2 phenotype (Fig.…”