Chaux P
Groupe de Recherche sur la Biologie et l'Immunologie Cellulaires des Cancers Digestifs, DIJON, France.
Pathol Biol (Paris). 1995 Dec;43(10):897-903.
In tumor cells, abnormal proteins expression results from DNA mutations or fusion associated with carcinogenesis or tumor progression. Those abnormal, often clearly defined proteins should be recognized by the immune system and induce an immune response leading to tumor rejection. Actually, most tumors escape the immune response through a specific tolerance, able to suppress or to modify the immune response against tumor associated antigens. Factors which contribute to tumor immunological escape are not elucidated, but could involve a defect in tumor-antigen presentation to the host immune system. An effective immune response against tumor requires tumor-associated antigens to be processed into immunogenic peptides which are presented to T lymphocytes in association with MHC molecules. T-cell fonctional activation requires also a costimulatory signal delivered to the CD28 receptor on T cells by the B7 family of molecules expressed by the antigen-presenting cells. Most tumor cells express MHC class I molecules, a minority also express MHC class II molecules and only a few lymphoma have been reported to express B7. So, tumor cells are not able to present efficiently their specific antigens to competent T cells. Most tumors are yet infiltrated by inflammatory cells, some of them possessing the capacity to process tumor antigens and to present them to competent T cells, either inside the tumor itself, or after migration into the draining lymph nodes. Among antigen-presenting cells, dendritic cells, unlike B lymphocytes and macrophages, are the only cells able to stimulate naive T lymphocytes. They present effectively antigens in situ and stimulate naive and memory T lymphocytes into secondary lymphoid organs. Actually, dendritic cells are supposed to take place in the antitumor immune response, and dendritic cells infiltration inside numerous neoplasms is often associated to an immune response against tumor. However, many questions still underline the failure to recognize stimuli involved in the mobilization (and the retention?) of dendritic cells inside tumor, or which incite them to migrate out of it to ensure their antigen presenting cell function effectively. The secretion of immunosuppressive factors like IL-10, either by tumor cells and by tumor-infiltrating leukocytes represents one of the mechanisms involved in the modulation of the antigen-presenting cell function and in tumor immunological escape. Recent works were undertaken to increase tumor cells immunogenicity. B7.1 molecule transfection allows tumor cells to present directly their antigens and leads to their eradication in vivo. Those results suggest that tumor-antigens presentation is limited in tumor-bearing hosts.
在肿瘤细胞中，异常蛋白质表达源于与致癌作用或肿瘤进展相关的DNA突变或融合。那些异常的、通常定义明确的蛋白质应被免疫系统识别，并诱导导致肿瘤排斥的免疫反应。实际上，大多数肿瘤通过一种特异性耐受逃避免疫反应，这种耐受能够抑制或改变针对肿瘤相关抗原的免疫反应。导致肿瘤免疫逃逸的因素尚未阐明，但可能涉及肿瘤抗原向宿主免疫系统呈递的缺陷。针对肿瘤的有效免疫反应需要将肿瘤相关抗原加工成免疫原性肽，这些肽与MHC分子结合后呈递给T淋巴细胞。T细胞的功能性激活还需要抗原呈递细胞表达的B7分子家族向T细胞上的CD28受体传递共刺激信号。大多数肿瘤细胞表达MHC I类分子，少数也表达MHC II类分子，据报道只有少数淋巴瘤表达B7。因此，肿瘤细胞无法有效地将其特异性抗原呈递给有功能的T细胞。大多数肿瘤仍被炎性细胞浸润，其中一些细胞具有处理肿瘤抗原并将其呈递给有功能的T细胞的能力，无论是在肿瘤内部，还是在迁移至引流淋巴结后。在抗原呈递细胞中，与B淋巴细胞和巨噬细胞不同，树突状细胞是唯一能够刺激初始T淋巴细胞的细胞。它们在原位有效呈递抗原，并在二级淋巴器官中刺激初始和记忆T淋巴细胞。实际上，树突状细胞被认为参与抗肿瘤免疫反应，并且许多肿瘤内的树突状细胞浸润通常与针对肿瘤的免疫反应相关。然而，许多问题仍然突出表明未能识别参与肿瘤内树突状细胞动员（以及滞留？）的刺激因素，或者未能识别促使它们从肿瘤中迁移出来以有效确保其抗原呈递细胞功能的因素。肿瘤细胞和肿瘤浸润白细胞分泌免疫抑制因子如IL-10是参与调节抗原呈递细胞功能和肿瘤免疫逃逸的机制之一。最近开展了一些工作来提高肿瘤细胞的免疫原性。B7.1分子转染使肿瘤细胞能够直接呈递其抗原，并导致其在体内被根除。这些结果表明，荷瘤宿主中肿瘤抗原的呈递是有限的。
