Somers S S
Academic Surgical Unit, St James's University Hospital, Leeds.
Ann R Coll Surg Engl. 1996 Mar;78(2):103-9.
The presence of immune infiltration of tumour deposits and the existence of effective in vitro anti-tumour immune responses would suggest the possibility of therapeutic manipulation against tumour cells. However, clinical immunotherapy has shown little promise as a cancer treatment. Numerous explanations for this inefficacy have been proposed, one of which involves the elaboration of immunosuppressive moieties from tumour cells. The results of studies presented below show that serum from patients with gastrointestinal and other tumours have immunosuppressive influences on normal lymphocytes. The degree of this in vitro inhibition is related to tumour 'bulk' and may reflect a systemic immunosuppressive influence of the tumour. Isolation and culture of lymphocytes from gastrointestinal tumour deposits demonstrated that these immune cells are functionally inert, suggesting the existence of an immunosuppressive tumour microenvironment. The isolation and partial purification of an immunosuppressive moiety from conditioned culture medium of a variety of human tumour cell lines further supports the hypothesis of tumour-mediated immunosuppression. A number of protein tumour cell products have been described with potent immunosuppressive properties. These include transforming growth factor-beta, interleukin-10, and the retroviral envelope protein p15E. The surgical implications of the proposed tumour-host immune relationship includes the hypothesis that clinically apparent disease may not be amenable to immune attack owing to tumour-mediated immune suppression. The use of immunostimulatory strategies as adjuvant perioperative therapy would seem a more effective environment for the activation of antitumour immune responses in the surgical patient.
肿瘤沉积物中存在免疫浸润以及有效的体外抗肿瘤免疫反应的存在,提示了针对肿瘤细胞进行治疗性干预的可能性。然而,临床免疫疗法作为一种癌症治疗方法几乎没有显示出前景。针对这种无效性已经提出了许多解释,其中之一涉及肿瘤细胞产生免疫抑制成分。以下研究结果表明,胃肠道肿瘤和其他肿瘤患者的血清对正常淋巴细胞具有免疫抑制作用。这种体外抑制的程度与肿瘤“体积”有关,可能反映了肿瘤的全身免疫抑制作用。从胃肠道肿瘤沉积物中分离和培养淋巴细胞表明,这些免疫细胞功能惰性,提示存在免疫抑制性肿瘤微环境。从多种人类肿瘤细胞系的条件培养基中分离和部分纯化一种免疫抑制成分,进一步支持了肿瘤介导的免疫抑制假说。已经描述了许多具有强大免疫抑制特性的蛋白质肿瘤细胞产物。这些包括转化生长因子-β、白细胞介素-10和逆转录病毒包膜蛋白p15E。所提出的肿瘤-宿主免疫关系的外科意义包括这样一种假说,即由于肿瘤介导的免疫抑制,临床上明显的疾病可能无法接受免疫攻击。使用免疫刺激策略作为围手术期辅助治疗似乎是在手术患者中激活抗肿瘤免疫反应的更有效环境。