Das angeborene Immunsystem beim Oropharynxkarzinom

Abstract

Based on clinical and experimental data, oropharyngeal squamous cell carcinomas (OPSCC) associated with human papillomavirus (HPV) have been recognized as a distinct entity of head and neck cancers. However, outside of clinical trials, HPV status currently has no impact on treatment. The natural replication cycle of HPV takes place in epithelial cells, and is thus spatially separated from cytotoxic immune cells in the epidermis. Dendritic cells (Langerhans cells, LC), however, are frequent in this upper dermal layer. The ability of LC to process antigens, migrate, and, ultimately activate T cells is inhibited by the activity of the viral oncoproteins (E5-E7). Downregulation of functional human leukocyte antigen I (HLA-I) epithelial cell surface expression contributes to LC inhibition. However, due to their absence in upper skin layers, corresponding activation of natural killer (NK) cells via missing-self recognition is not relevant. Genome-wide analyses have revealed specific expression signatures for HPV-associated OPSCC that are distinct from HPV-negative cancers. Interestingly, aberrations in HLA-I genes were common in HPV-associated OPSCC. Our own findings indicate more frequent infiltration of HPV-associated OPSCC by CD56-positive (CD56) NK cells, which might be related to HLA-I downregulation during HPV-associated carcinogenesis. In patients with OPSCC, CD56 positivity correlates with improved prognosis after conventional therapy. This could be evidence for HPV-associated OPSCC being especially eligible for novel immune-based therapies and an indication that immunological data should be included in the design of clinical trials.

Immune Responses in Oral Papillomavirus Clearance in the MmuPV1 Mouse Model

“…Since both male and female B6 and genetically modified mice showed strong immune control of viral infections leading to viral clearance, we next determined whether both sexes use the same immune strategy to control viral infections. Innate immune responses have been reported to play an important role in controlling HPV infections in humans, especially in the early stage of viral infection [25,41,59]. A previous study using the mouse genital infection model also demonstrated the involvement of several innate immune pathways in MmuPV1 infection [20].…”

“…pDCs have been targeted for treating HPV-associated cancer [38]. Other immune cells, including macrophages and neutrophils, are also important players in innate and adaptive immune responses [39][40][41]. Tumor-infiltrating lymphocytes have been reported valuable in predicting the outcome of HPV-positive OPC [42,43].…”

Update: Epidemiologie und Prävention des Oropharynxkarzinoms

“…Rein HPV-assoziierte Tumoren zeigen häufig einen hornarmen, an ein basaloides Plattenepithelkarzinom erinnernden histologischen Phänotyp, ohne jedoch der Subgruppe der basaloiden Plattenepithelkarzinome im engeren Sinne zugehörig zu sein. HPV-Proteine führen außerdem zu einem "immune escape", welcher die chronische Infektion und damit die mögliche maligne Entartung wahrscheinlicher macht [37,38], wobei die 1-malige Infektion mit HPV nicht zwingend zu einer malignen Entartung führt.…”