Szczepański Mirosław, Stelmachowska Maria, Stryczyński Lukasz, Golusiński Wojciech, Samara Husam, Mozer-Lisewska Iwona, Zeromski Jan
Department of Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland.
Eur Arch Otorhinolaryngol. 2007 May;264(5):525-30. doi: 10.1007/s00405-006-0215-7. Epub 2006 Dec 13.
Head and neck cancers remain a big challenge for oncology. Among them laryngeal carcinomas predominate. In spite of abundant inflammatory cell infiltrates containing several immunologically competent cells, patients with head and neck cancers show markedly suppressed anti-tumor response. In general, cancer cells use strategies to avoid recognition and destruction by the immune system. Toll-like receptors 1-13 (TLRs) are crucial for activation of innate immunity and secondarily for the induction of acquired response. TLRs are mainly expressed on cells of the immune system, but they have been demonstrated on endothelial and epithelial cells. Ligand binding to TLR leads to the activation of several genes, predominantly proinflammatory ones such as IL-1 and TNF-alpha and maturation of professional antigen presenting cells (APC) i.e., dendritic cells. It can cause better tumor antigen presentation by APC. The aim of this study was the evaluation of expression of TLR-2, TLR-3 and TLR-4 in the microenvironment of laryngeal carcinoma. Tumor specimens (n = 20, male patients aged 43-77 years, mean 57 years) from patients subjected to total laryngectomy. Immunohistochemistry and indirect immunoflourescence on frozen tissue sections. Cancer tissue: portion of cancer cells manifested membrane and/or cytoplasmic expression of TLR-2, TLR-3 and TLR-4. The most frequent expression on tumor cells was TLR-2 and the least expression of TLR-4. Inflammatory infiltrates: in all cases inflammatory cell infiltrates of various intensities were present, both in tumor mass and tumor stroma. Expression of all TLRs tested, both, membrane and cytoplasmic ones were shown on inflammatory cells, but distinct in quantitative terms. TLR-4 positive cells were the most frequent. A portion of cells expressed both, TLR and HLA-DR. It is of interest that TLRs tested were expressed not only on cells of inflammatory infiltrate, but also on tumor cells. This fact may be an important factor in tumor escape from immune surveillance. It is notable, that both, TLRs and HLA-DR were shown to be co-expressed, what may favor the role and impact of TLRs in antigen presentation. Further studies are needed to elucidate TLRs function in the course of neoplastic process.
头颈癌仍然是肿瘤学面临的一大挑战。其中喉癌最为常见。尽管头颈部癌症患者的炎症细胞浸润丰富,包含多种具有免疫活性的细胞,但其抗肿瘤反应却明显受到抑制。一般来说,癌细胞会采取策略来逃避免疫系统的识别和破坏。Toll样受体1 - 13(TLRs)对于激活先天免疫至关重要,其次对于诱导获得性免疫反应也很关键。TLRs主要在免疫系统细胞上表达,但也已在血管内皮细胞和上皮细胞上得到证实。配体与TLR结合会导致多个基因的激活,主要是促炎基因,如白细胞介素 - 1和肿瘤坏死因子 - α,并使专职抗原呈递细胞(APC)即树突状细胞成熟。它可使APC更好地呈递肿瘤抗原。本研究的目的是评估TLR - 2、TLR - 3和TLR - 4在喉癌微环境中的表达。取自接受全喉切除术患者的肿瘤标本(n = 20,男性患者,年龄43 - 77岁,平均57岁)。对冷冻组织切片进行免疫组织化学和间接免疫荧光检测。癌组织:部分癌细胞表现出TLR - 2、TLR - 3和TLR - 4的膜和/或细胞质表达。肿瘤细胞上最常见的表达是TLR - 2,TLR - 4的表达最少。炎症浸润:在所有病例中,肿瘤块和肿瘤基质中均存在不同强度的炎症细胞浸润。所检测的所有TLRs,包括膜性和细胞质性的,在炎症细胞上均有表达,但在数量上有所不同。TLR - 4阳性细胞最为常见。一部分细胞同时表达TLR和HLA - DR。有趣的是,所检测的TLRs不仅在炎症浸润细胞上表达,也在肿瘤细胞上表达。这一事实可能是肿瘤逃避免疫监视的一个重要因素。值得注意的是,TLRs和HLA - DR均显示为共表达,这可能有利于TLRs在抗原呈递中的作用和影响。需要进一步研究以阐明TLRs在肿瘤发生过程中的功能。