Tumor Microenvironment, HLA Class I and APM Expression in HPV-Negative Oral Squamous Cell Carcinoma

• Published in: Cancers Vol. 13; no. 4; p. 620
• Main Authors: Wickenhauser, Claudia, Bethmann, Daniel, Kappler, Matthias, Eckert, Alexander Walter, Steven, André, Bukur, Jürgen, Fox, Bernard Aloysius, Beer, Jana, Seliger, Barbara
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.02.2021; MDPI
• Subjects: Antibodies; Antigen processing; antigen processing machinery; Antigens; Cancer therapies; CD8 antigen; Chemotherapy; Cytotoxicity; Disease; FDA approval; Foxp3 protein; Genotype & phenotype; Histocompatibility antigen HLA; HLA class I; Human papillomavirus; immune cell infiltration; immune escape; Immunomodulation; Immunosurveillance; Immunotherapy; Janus kinase; Lymphocytes; Lymphocytes T; Medical prognosis; Metastases; Molecular modelling; Oral squamous cell carcinoma; Phenotypes; prognosis; Squamous cell carcinoma; Tumor cells; Tumor microenvironment; Tumors; γ-Interferon; HLA class I; immune escape; oral squamous cell carcinoma; immune cell infiltration; prognosis; antigen processing machinery
• ISSN: 2072-6694; 2072-6694
• 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.