T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-Ts) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for the optimization of their use with combination or consolidation strategies, which necessitates the prognostic stratification of patients. While traditional clinical prognostic factors identified in the era of chemotherapy are characterized by limited value, the tumor microenvironment (TME) is becoming a new prognostic cluster. We examine how the heterogeneity of LBCL, characterized by variations in tumor parameters and differences in TME immune cell composition, immune checkpoint expression, and cytokine milieu, correlates with both positive responses and resistance to treatment. While classical parameters such as histological subtype, cell of origin, and target antigen expression lack proven prognostic value for T-cell redirecting therapies, the density and functional state of tumor-infiltrating lymphocytes, tumor-associated macrophages, and immune checkpoint molecules are shown to be critical determinants of therapeutic success, particularly in CAR-T therapy. We identify several gaps in the current knowledge and suggest that the insights gained from CAR-T experience could be instrumental in refining BSA applications. This report also highlights limitations in the current knowledge, as TME data derive from a limited number of registrational trials with varying methodologies, complicating cross-study comparisons and often focusing on immediate response metrics rather than long-term outcomes. By dissecting the complex interactions within the TME, this review aims to identify new prognostic factors and targets, ultimately fostering more effective and tailored treatment strategies for LBCL patients.
T细胞重定向疗法，包括嵌合抗原受体T细胞（CAR-T）和双特异性抗体（BSA），已彻底改变了复发/难治性大B细胞淋巴瘤（LBCL）的治疗。随着这些先进疗法临床经验的积累，通过联合或巩固策略优化其应用的潜力日益显现，这使得患者预后分层变得至关重要。传统化疗时代确定的临床预后因素价值有限，而肿瘤微环境（TME）正成为一个新的预后评估维度。本文探讨了LBCL的异质性——表现为肿瘤参数差异以及TME中免疫细胞组成、免疫检查点表达和细胞因子环境的不同——如何与治疗的正向反应及耐药性相关联。虽然组织学亚型、细胞起源和靶抗原表达等经典参数对T细胞重定向疗法缺乏明确的预后价值，但肿瘤浸润淋巴细胞、肿瘤相关巨噬细胞的密度与功能状态以及免疫检查点分子已被证明是治疗成功的关键决定因素，尤其在CAR-T疗法中。我们指出了当前认知中的若干空白，并认为从CAR-T经验中获得的见解可能有助于优化BSA的应用。本报告也强调了现有知识的局限性：TME数据来源于少数注册试验，且研究方法各异，这使跨研究比较变得复杂，并往往侧重于短期疗效指标而非长期结局。通过剖析TME内的复杂相互作用，本综述旨在识别新的预后因素和治疗靶点，最终为LBCL患者制定更有效、更个体化的治疗策略。
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