Maglioco Andrea, Machuca Damián G, Camerano Gabriela, Costa Héctor A, Ruggiero Raúl, Dran Graciela I
Laboratorio de Oncología Experimental, IMEX-CONICET-ANM, Academia Nacional de Medicina, Buenos Aires, Argentina. E-mail:
Medicina (B Aires). 2014;74(3):185-8.
In cancer, B cells have been classically associated with antibody secretion, antigen presentation and T cell activation. However, a possible role for B lymphocytes in impairing antitumor response and collaborating with tumor growth has been brought into focus. Recent reports have described the capacity of B cells to negatively affect immune responses in autoimmune diseases. The highly immunogenic mouse tumor MCC loses its immunogenicity and induces systemic immune suppression and tolerance as it grows. We have previously demonstrated that MCC growth induces a distinct and progressive increase in B cell number and proportion in the tumor draining lymph nodes (TDLN), as well as a less prominent increase in T regulatory cells. The aim of this research was to study B cell characteristics and function in the lymph node draining MCC tumor and to analyze whether these cells may be playing a role in suppressing antitumor response and favoring tumor progression. Results indicate that B cells from TDLN expressed increased CD86 and MHCII co-stimulatory molecules indicating activated phenotype, as well as intracellular IL-10, FASL and Granzyme B, molecules with regulatory immunosuppressive properties. Additionally, B cells showed high inhibitory upon T cell proliferation ex vivo, and a mild capacity to secrete antibodies. Our conclusion is that even when evidence of B cell-mediated activity of the immune response is present, B cells from TDLN exhibit regulatory phenotype and inhibitory activity, probably contributing to the state of immunological tolerance characteristic of the advanced tumor condition.
在癌症中，B细胞传统上与抗体分泌、抗原呈递和T细胞活化相关。然而，B淋巴细胞在损害抗肿瘤反应和与肿瘤生长协同作用方面的潜在作用已成为焦点。最近的报道描述了B细胞在自身免疫性疾病中对免疫反应产生负面影响的能力。高度免疫原性的小鼠肿瘤MCC在生长过程中会失去其免疫原性，并诱导全身免疫抑制和耐受。我们之前已经证明，MCC的生长会导致肿瘤引流淋巴结（TDLN）中B细胞数量和比例显著且逐渐增加，以及调节性T细胞数量略有增加。本研究的目的是研究引流MCC肿瘤的淋巴结中B细胞的特征和功能，并分析这些细胞是否可能在抑制抗肿瘤反应和促进肿瘤进展中发挥作用。结果表明，来自TDLN的B细胞表达增加的共刺激分子CD86和MHCII，表明其具有活化表型，同时还表达细胞内IL-10、FASL和颗粒酶B，这些分子具有调节性免疫抑制特性。此外，B细胞在体外对T细胞增殖具有高度抑制作用，并且具有轻微的抗体分泌能力。我们的结论是，即使存在B细胞介导的免疫反应活性的证据，来自TDLN的B细胞仍表现出调节性表型和抑制活性，这可能导致晚期肿瘤状态下的免疫耐受状态。
