The activated B-cell-like subtype of diffuse large B-cell lymphoma (ABC-DLBCL) displays a worse outcome than the germinal center B-cell-like subtype (GCB-DLBCL). Currently, targeting tumor microenvironment (TME) is the promising approach to cure DLBCL with profound molecular heterogeneity, however, the factors affecting the tumor-promoting TME of ABCDLBCL are elusive. Here, cytokine interleukin-16 (IL-16) is expressed in tumor cells of ABCDLBCL and secreted by the cleavage of active caspase-3. The serum IL-16 levels are not only a sensitive marker of treatment response but also positively correlated with unfavorable prognosis in DLBCL patients. While IL-16 shows few direct promotional effects on tumor cell growth in vitro, its bioactive form significantly promotes tumor progression in vivo. Mechanically, IL-16 increases the infiltration of macrophages by the chemotaxis of CD4+ monocytes in the TME enhancing angiogenesis, and the expression of cytokine IL-6 and IL-10, as well as decreasing T cell infiltration to accelerate tumor progression. This study demonstrates that IL-16 exerts a novel role in coordinating the bidirectional interactions between tumor progression and the TME. IMM0306, a fusion protein of CD20 mAb with the CD47 binding domain of SIRPα, reverses the tumorpromoting effects of IL-16,which provides new insight into treatment strategy in ABC-DLBCL.

中文翻译：

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淋巴瘤细胞驱动的 IL-16 在活化的 B 细胞样弥漫性大 B 细胞淋巴瘤中表达，并调节促肿瘤微环境。


弥漫性大 B 细胞淋巴瘤 (ABC-DLBCL) 的活化 B 细胞样亚型表现出比生发中心 B 细胞样亚型 (GCB-DLBCL) 更差的结果。目前，靶向肿瘤微环境（TME）是治疗具有深刻分子异质性的 DLBCL 的有前途的方法，然而，影响 ABCDLBCL 肿瘤促进 TME 的因素尚不清楚。在此，细胞因子白细胞介素-16 (IL-16) 在 ABCDLBCL 的肿瘤细胞中表达，并通过活性 caspase-3 的裂解而分泌。血清IL-16水平不仅是治疗反应的敏感标志，而且与DLBCL患者的不良预后呈正相关。虽然 IL-16 在体外对肿瘤细胞生长几乎没有直接促进作用，但其生物活性形式在体内显着促进肿瘤进展。从机械角度而言，IL-16 通过 TME 中 CD4+ 单核细胞的趋化作用增加巨噬细胞的浸润，增强血管生成以及细胞因子 IL-6 和 IL-10 的表达，并减少 T 细胞浸润以加速肿瘤进展。这项研究表明 IL-16 在协调肿瘤进展和 TME 之间的双向相互作用方面发挥着新的作用。 IMM0306是CD20 mAb与SIRPα的CD47结合域的融合蛋白，可逆转IL-16的促癌作用，为ABC-DLBCL的治疗策略提供了新的见解。