Wickenhauser Claudia, Bethmann Daniel, Kappler Matthias, Eckert Alexander Walter, Steven André, Bukur Jürgen, Fox Bernard Aloysius, Beer Jana, Seliger Barbara
Institute of Pathology, University Hospital Halle (Saale), 06112 Halle (Saale), Germany.
Department of Oral, Maxillofacial and Plastic Surgery, University Hospital Halle (Saale), 06120 Halle (Saale), Germany.
Cancers (Basel). 2021 Feb 4;13(4):620. doi: 10.3390/cancers13040620.
Progression of oral squamous cell carcinoma (OSCC) has been associated with an escape of tumor cells from the host immune surveillance due to an increased knowledge of its underlying molecular mechanisms and its modulation by the tumor microenvironment and immune cell repertoire. In this study, the expression of HLA class I (HLA-I) antigens and of components of the antigen processing machinery (APM) was analyzed in 160 pathologically classified human papilloma virus (HPV)-negative OSCC lesions and correlated to the intra-tumoral immune cell response, IFN-γ signaling and to the patient's outcome. A heterogeneous but predominantly lower constitutive protein expression of HLA-I APM components was found in OSCC sections when compared to non-neoplastic cells. Tumoral HLA-I APM component expression was further categorized into the three major phenotypes HLA-I/APM, HLA-I/APM and HLA-I/APM. In the HLA-I/APM group, the highest frequency of intra-tumoral CD8 T cells and lowest number of CD8 T cells close to FoxP3 cells were found. Patients within this group presented the most unfavorable survival, which was significantly evident in stage T2 tumors. Despite a correlation with the number of intra-tumoral CD8 T cells, tumoral JAK1 expression as a surrogate marker for IFN-γ signaling was not associated with HLA-I/APM expression. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.
口腔鳞状细胞癌（OSCC）的进展与肿瘤细胞逃避宿主免疫监视有关，这是由于对其潜在分子机制以及肿瘤微环境和免疫细胞库对其调节的认识不断增加。在本研究中，分析了160例经病理分类的人乳头瘤病毒（HPV）阴性OSCC病变中HLA I类（HLA-I）抗原和抗原加工机制（APM）成分的表达，并将其与肿瘤内免疫细胞反应、IFN-γ信号传导以及患者预后相关联。与非肿瘤细胞相比，在OSCC切片中发现HLA-I APM成分的组成性蛋白表达存在异质性但主要较低。肿瘤HLA-I APM成分表达进一步分为三种主要表型HLA-I/APM、HLA-I/APM和HLA-I/APM。在HLA-I/APM组中，肿瘤内CD8 T细胞频率最高，靠近FoxP3细胞的CD8 T细胞数量最少。该组患者的生存率最不理想，在T2期肿瘤中尤为明显。尽管与肿瘤内CD8 T细胞数量相关，但作为IFN-γ信号替代标志物的肿瘤JAK1表达与HLA-I/APM表达无关。因此，本研究结果强烈表明，在HPV阴性OSCC的免疫调节过程中存在其他因素，在该肿瘤实体中，可能存在一个超出HLA-I/APM成分和T细胞浸润的、与肿瘤负荷相关的复杂免疫逃逸机制网络。
