IL-33/ST2 signaling promotes constitutive and inductive PD-L1 expression and immune escape in oral squamous cell carcinoma.

Background: Loss-of-function of PD-L1 induces therapy resistance of anti-PD-1/L1 therapy, and the complex regulatory mechanisms are not completely understood. We previously reported that stroma-derived interleukin-33 (IL-33) promoted the progression of oral squamous cell carcinoma (OSCC). We here focused on the immune-regulation role of IL-33 and its receptor ST2 signaling in PD-L1-positive OSCC patients.

OXTR stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling.

The Pattern Of Invasion (POI) of tumor cells into adjacent normal tissues clinically predicts postoperative tumor metastasis/recurrence of early oral squamous cell carcinoma (OSCC), but the mechanisms underlying the development of these subtypes remain unclear. Focusing on the highest score of POIs (Worst POI, WPOI) present within each tumor, we observe a disease progression-driven shift of WPOI towards the high-risk type 4/5, associated with a mesenchymal phenotype in advanced OSCC. WPOI 4-5-derived cancer-associated fibroblasts (CAFs), characterized by high oxytocin receptor expression (OXTR), contribute to local-regional metastasis.

Worst Pattern of Perineural Invasion Redefines the Spatial Localization of Nerves in Oral Squamous Cell Carcinoma.

As a key histopathological characteristic of tumor invasion, perineural invasion (PNI) assists tumor dissemination, whereas the current definition of PNI by dichotomy is not accurate and the prognostic value of PNI has not reached consensus. To define PNI status in each patient when mixed types of PNI occurred simultaneously, we here further subclassified the traditional PNI in 183 patients with oral squamous cell carcinoma (OSCC). The spatial localization of nerves in OSCC microenvironment was thoroughly evaluated and successfully concluded into four types of PNI: 0, tumor cells away from nerves; 1, tumor cells encircling nerves less than 33%; 2, tumor cells encircling nerves at least 33%; and 3, tumor cells infiltrating into nerve sheathes.

Functional Heterogeneity of Reelin in the Oral Squamous Cell Carcinoma Microenvironment.

Background: Reelin, an extracellular glycoprotein, is expressed on neuronal cells and participates in neuronal migration during brain development. Recently, Reelin also has a vital role in carcinogenesis. However, its role in oral squamous cell carcinoma (OSCC) remains to be explored.

CD38 Multi-Functionality in Oral Squamous Cell Carcinoma: Prognostic Implications, Immune Balance, and Immune Checkpoint.

Background: CD38 belongs to the ribosyl cyclase family and is expressed on various hematological cells and involved in immunosuppression and tumor promotion. Although targeting CD38 antibodies has been approved for treatment of multiple myeloma, the function of CD38 in solid tumor, oral squamous cell carcinoma (OSCC) , has not been investigated.

Methods: This retrospective study included 92 OSCC samples and analyzed the spatial distribution of CD38 by immunohistochemistry (IHC).

The KiSS-1/GPR54 system: Essential roles in physiological homeostasis and cancer biology.

first identified as an anti-metastasis gene in melanoma, encodes C-terminally amidated peptide products, including kisspeptin-145, kisspeptin-54, kisspeptin-14, kisspeptin-13 and kisspeptin-10. These products are endogenous ligands coupled to G protein-coupled receptor 54 (GPR54)/hOT7T175/AXOR12. To date, the regulatory activities of the KiSS-1/GPR54 system, such as puberty initiation, antitumor metastasis, fertility in adulthood, hypothalamic-pituitary-gonadal axis (HPG axis) feedback, and trophoblast invasion, have been investigated intensively.

The balance of serum IL-18/IL-37 levels is disrupted during the development of oral squamous cell carcinoma.

Growing evidences have demonstrated a pivotal role of chronic inflammation in oral squamous cell carcinoma (OSCC) through the modulation of inflammatory cells and cytokine production. IL-37 is newly discovered anti-inflammatory member of IL-1 family and can bind to IL-18 receptor to inhibit IL-18 (pro-inflammatory member of IL-1 family) function. Investigation on the balance of IL-18/IL-37 would provide new insights into the function of IL-1 family in OSCC.

Aberrant Expression Of PDCD4/eIF4A1 Signal Predicts Postoperative Recurrence For Early-Stage Oral Squamous Cell Carcinoma.

Background: Programmed cell death 4 () as a tumor suppressor gene inhibits growth and metastasis of cancer cells, which involved with eIF4A1, the inhibitor of translation initiation. Although the prognosis of early-stage oral squamous cell carcinoma (OSCC) is generally better, but many patients occur recurrence after surgery. Understanding the clinical expression pattern of PDCD4/eIF4A1 signal would provide diagnostic biomarker and target therapy premise for early-stage OSCC patients.

Tumor-infiltrating lymphocyte-derived MLL2 independently predicts disease-free survival for patients with early-stage oral squamous cell carcinoma.

Background: MLL2 (mixed-lineage leukemia 2) is recognized as an essential role in regulating histone 3 lysine 4 tri-methylation (H3K4me3) in mammalian cells. It is frequently mutated to promote developmental diseases and tumor initiation. However, the expression pattern of MLL2 and its clinical significance for patients with early-stage oral squamous cell carcinoma (OSCC) remain totally unknown.

The Regulatory Role of Non-coding RNAs on Programmed Cell Death Four in Inflammation and Cancer.

Programmed cell death 4 (PDCD4) is a tumor suppressor gene implicated in many cellular functions, including transcription, translation, apoptosis, and the modulation of different signal transduction pathways. The downstream mechanisms of PDCD4 have been well-discussed, but its upstream regulators have not been systematically summarized. Noncoding RNAs (ncRNAs) are gene transcripts with no protein-coding potential but play a pivotal role in the regulation of the pathogenesis of solid tumors, cardiac injury, and inflamed tissue.

Clear Cell Odontogenic Carcinoma: a Clinicopathological and Immunocytochemical Analysis.

Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic tumor associated with aggressive clinical behavior, metastasis and low survival. To date, only 67 cases have been described in the English language literature, and an understanding of the behavior of CCOC has been based on limited case reports. The aim of the research was to further reveal the features of CCOC.