Immunomodulatory aspects in the progression and treatment of oral malignancy

Inflammation substantially affects the risk of oral malignancy. Pro-inflammatory cytokine, interferon (IFN)-γ, confers anti-tumor activity using several different mechanisms. Conversely, higher expression of interleukin (IL)-17 is associated with worse prognosis. Monocyte chemotactic protein (MCP)-1 correlates positively with poor long-term survival of head and neck squamous cell carcinoma (HNSCC) patients. IL-1α affects cancer associated fibroblasts and macrophages, and promote several malignant phenotypes including immune suppression. Some anti-inflammatory cytokines, including IL-10 and transforming growth factor (TGF)-β, relate to pro-tumoral activities.Among immune checkpoint modulators, programmed death (PD-)1 and PD-ligand (L)1 facilitate oral squamous cell carcinoma (OSCC) cell evasion from immune surveillance, and the expression status of these has a prognostic value.OSCCs contain tumor associated macrophages (TAMs) as major stromal cells of their tumor microenvironment. Among the two distinctive states, M2 macrophages support tumor invasion, metastasis and immune suppression. Crosstalk between TAMs and OSCC or cancer-associated fibroblasts (CAF) plays an important role in the progression of OSCC.Clinical trials with blocking antibodies against IL-1α or melanoma-associated antigens have been reported as therapeutic approaches against OSCCs. The most promising approach activating antitumor immunity is the blockade of PD-1/PD-L1 axis. Manipulating the polarization of pro-tumorigenic macrophages has been reported as a novel therapeutic approach.     

Biliary adenofibroma with ominous features of imminent malignant changes

Biliary adenofibroma (BAF) is a rare, benign liver tumor. Herein, we report a case of BAF with histological features of imminent malignant changes. Ultrasound and CT revealed a solid 2.5-cm mass in the right liver lobe. The patient was asymptomatic and had no past medical history including liver disease. A general examination that included the abdomen and the laboratory data were normal. Because of the increase of its size, this tumor was surgically resected. Grossly, a 3.5-cm nodular mass abutted on the hepatic capsule was found, and its cut surface showed a well-circumscribed, whitish, and firm lesion that showed microcystic changes in the periphery and solid changes in the central parts. Histologically, the tumor showed a proliferation of tubulocystic structures embedded in a fibrous stroma. Microcysts were prevalent in the periphery, while tubular components with abundant fibrous stroma were in the central parts. The tubules were variably dilated and branched. This case closely resembled the previously reported cases of BAF, except that there were complicated papillary projections with fine fibrovascular cores in some of the microcysts and that the epithelial component in papillary projections showed dysplastic changes and increased cellular proliferative activities, implicating ominous features of imminent malignant changes. These dysplastic and papillary changes may be an intermediate lesion leading to malignancy, which have occasionally been reported in BAF.