Department of Medicine, Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
Curr Hematol Malig Rep. 2018 Feb;13(1):37-43. doi: 10.1007/s11899-018-0437-y.
T-cells and natural killer (NK) cells share the same ontogeny, and lymphomas derived from them are clinically diverse, occurring in nodal and extranodal sites. In addition to inherent properties of these lymphomas, their microenvironment also impacts on pathogenesis and response to therapy. An understanding of the milieu of T-cell and NK cell lymphomas has important implications on treatment.
Components of the microenvironment include tumour-associated macrophages (TAM), non-neoplastic T-cells and B-cells, eosinophils, dendritic cells, endothelial cells and blood vessels. TAM typically undergoes M2 polarization, promoting angiogenesis and inhibiting anti-tumour cellular immunity. In lymphomas of follicular helper T-cell derivation, increased B-cell proliferation occurs, which may in turn enhance neoplastic T-cell growth. The expression of immune checkpoint ligands on TAM, dendritic cells or lymphoma cells induces an immunosuppressive environment conducive to neoplastic proliferation. Strategies against this complex cellular and immunologic microenvironment have shown promises. These include the use of signal transduction inhibitors, monoclonal antibodies against chemokines or non-neoplastic microenvironmental cells, immunomodulatory drugs and immune checkpoint blockade. As T-cell and NK cell lymphomas are highly heterogeneous, clinical trials to demonstrate efficacy of a given therapeutic approach requires careful design aiming at enriching patient populations who will best respond. Targeting of the immunologic milieu in T-cell and NK-cell lymphomas offers exciting challenges and opportunities.
T 细胞和自然杀伤 (NK) 细胞具有相同的起源，它们衍生的淋巴瘤在临床上具有多样性，发生在淋巴结和结外部位。除了这些淋巴瘤的固有特性外，其微环境也会影响发病机制和对治疗的反应。了解 T 细胞和 NK 细胞淋巴瘤的微环境具有重要的治疗意义。
微环境的组成部分包括肿瘤相关巨噬细胞 (TAM)、非肿瘤性 T 细胞和 B 细胞、嗜酸性粒细胞、树突状细胞、内皮细胞和血管。TAM 通常经历 M2 极化，促进血管生成并抑制抗肿瘤细胞免疫。在滤泡辅助 T 细胞衍生的淋巴瘤中，B 细胞增殖增加，这反过来又可能增强肿瘤性 T 细胞的生长。TAM、树突状细胞或淋巴瘤细胞上免疫检查点配体的表达诱导有利于肿瘤增殖的免疫抑制环境。针对这种复杂的细胞和免疫微环境的策略已经显示出了希望。这些策略包括使用信号转导抑制剂、针对趋化因子或非肿瘤性微环境细胞的单克隆抗体、免疫调节药物和免疫检查点阻断。由于 T 细胞和 NK 细胞淋巴瘤高度异质性，为了证明特定治疗方法的疗效，临床试验需要精心设计，旨在丰富最有可能产生反应的患者群体。针对 T 细胞和 NK 细胞淋巴瘤的免疫微环境具有令人兴奋的挑战和机遇。
