Background: Diffuse large B-cell lymphoma (DLBCL) is characterized by its clinical and biological heterogeneity. The clinical prognostic implications of tumor-associated macrophages (TAMs) in DLBCL remain controversial and the correlation between TAMs and peripheral absolute monocyte count (AMC) has not yet been elucidated. Methods: In 221 untreated, newly diagnosed patients with DLBCL, we evaluated the prognostic value of TAMs using immunohistochemical analysis, as well as the association of TAMs and AMC. Results: We found that high CD68 or high CD163 expression was correlated with clinicopathological characteristics, high CD163 expression was an adverse predictor for both overall survival (OS) [hazard ratio (HR) = 2.265, P = 0.005] and progression- free survival (PFS) (HR = 1.925, P = 0.017) in patients with DLBCL. Patients with high CD68 or high CD163 expression had significantly poorer OS and PFS than those with low CD68 or low CD163 expression, respectively (CD68: OS: P<0.001, PFS: P<0.001; CD163: OS: P<0.001, PFS: P<0.001), even in the rituximab era. Moreover, high-risk patients could be further identified by the expression of CD68 or CD163, especially in those classified as low/intermediate risk by International Prognostic Index (IPI). Furthermore, the significant positive correlation was also detected between CD68 expression or CD163 expression and AMC (r = 0.256, P<0.001; r = 0.303, P<0.001). Conclusions: Patients with high expression of TAMs tend to have poorer OS and PFS, even in the rituximab era, and have positive correlation with AMC. Therefore, the peripheral AMC is a useful prognostic marker reflecting the status of the tumor microenvironment (TME) in DLBCL.

Despite the use of modern immunochemotherapy regimens, a significant proportion of diffuse large B-cell lymphoma (DLBCL) patients will relapse. We proposed absolute lymphocyte count/absolute monocyte count ratio (ALC/AMC ratio) as a new prognostic factor in relapsed or primary refractory DLBCL.

Background: Epstein-Barr virus (EBV) is an oncovirus belonging to the herpesvirus family, associated with the pathogenesis of multiple malignancies, particularly Burkitt lymphoma (BL). The virus remains latent in host cells and plays a critical role in tumor progression through various mechanisms. A key glycoprotein, gp350, expressed during the lytic phase of EBV, is instrumental in viral entry into B cells and presents a unique antigenic target, making it a promising candidate for immunotherapeutic approaches, such as chimeric antigen receptor T-cell (CAR-T) therapy. Methods: In this study, we engineered CAR-T cells targeted against the gp350 glycoprotein and assessed their therapeutic potential through a series of in vitro and in vivo experiments. The efficacy of the gp350-CAR-T cells was evaluated by comparing their cytotoxic effects against both EBV-positive and -negative tumor cell lines. We utilized a xenograft model of Burkitt lymphoma to monitor the impact of gp350-CAR-T cell administration on tumor progression and overall survival. Results: The engineered gp350-CAR-T cells demonstrated potent cytotoxicity specifically against EBV-positive tumor cell lines. In our in vivo xenograft model, administration of gp350-CAR-T cells resulted in significant inhibition of tumor growth, highlighting their capability to effectively target and eliminate EBV-positive lymphomas. This selectivity underscores the potential of utilizing gp350 as a specific target for immunotherapy. Conclusion: Our findings advocate for the clinical application of gp350-directed CAR-T therapy as a prospective treatment strategy for patients with relapsed or refractory EBV-positive tumors. Given the encouraging preclinical results, further research is warranted to optimize CAR-T cell production processes and extend the potential of this therapy to other EBV-associated malignancies, paving the way for improved outcomes in affected patient populations.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive hematological malignancy with restricted effective therapy choices. Neither the recruitment of monocytes nor the functioning of the physiological mechanisms of macrophage polarization can be achieved without the involvement of the MCP-1/CCR2 axis. We investigated the feasibility of treatment targeting MCP-1-CCR2-macrophages axis in DLBCL. MCP-1, CD68, CD163 expression was analyzed by immunohistochemistry in 143 DLBCL patients tissues, and MCP-1 concentration and CD14 + CCR2 + monocytes in peripheral blood were analyzed in another cohort by enzyme linked immunosorbent assay or flow cytometry. THP-1 or U937 cells were used to mimic macrophages polarization with or without the blockade of MCP-1/CCR2 axis in vitro. BALB/C mice subcutaneous tumors were evaluated and detected after blocking MCP-1/CCR2 axis with CCR2 antagonist. MCP-1, CD68, CD163 expression and proportion of CD14 + CCR2 + monocytes in peripheral blood are prognostic for DLBCL patients. MCP-1 expression is positively associated with CD68 or CD163 expression in DLBCL. CCR2 antagonist intervention produces a blocking effect on the MCP-1/CCR2 signaling axis. This not only significantly inhibits monocyte recruitment in vitro and hinders the polarization of M2 macrophages toward a pro-tumorigenic phenotype, but also stimulates CD8 + T cell expansion. Under the synergistic effect of multiple mechanisms, the growth process of subcutaneous tumor was effectively suppressed. MCP-1-CCR2-M2 macrophages polarization plays vital roles in DLBCL progression. The results demonstrate the translational potential of MCP-1/CCR2 blockade for treatment of DLBCL.