Oral Lichen Planus as a Preneoplastic Inflammatory Model

Oral lichen planus (OLP) is a chronic oral inflammatory disease of unknown etiology. According to reports, 1-2% of OLP patients develop oral squamous cell carcinoma (OSCC) in the long run. While World Health Organization (WHO) classifies OLP as “a potentially malignant disorder,” it is still a matter of debate which mechanisms drive OLP to such a condition. The current hypothesis connecting OLP and OSCC is that chronic inflammation results in crucial DNA damage which over time results in cancer development. Initial studies investigating the OLP and OSCC link were mainly retrospective clinical studies. Over the past years, several amount of information has accumulated, mainly from molecular studies on the OLP malignant potential. This article is a critical review of whether OLP has a malignant potential and, therefore, represents a model of preneoplastic inflammation

Immunological synapse formation between T regulatory cells and cancer-associated fibroblasts promotes tumour development

Cancer-associated fibroblasts (CAFs) have emerged as a dominant non-hematopoietic cell population in the tumour microenvironment, serving diverse functions in tumour progression. However, the mechanisms via which CAFs influence the anti-tumour immunity remain poorly understood. Here, using multiple tumour models and biopsies from cancer patients, we report that α-SMA+ CAFs can form immunological synapses with Foxp3+ regulatory T cells (Tregs) in tumours. Notably, α-SMA+ CAFs can phagocytose and process tumour antigens and exhibit a tolerogenic phenotype which instructs movement arrest, activation and proliferation in Tregs in an antigen-specific manner. Moreover, α-SMA+ CAFs display double-membrane structures resembling autophagosomes in their cytoplasm. Single-cell transcriptomic data showed an enrichment in autophagy and antigen processing/presentation pathways in α-SMA-expressing CAF clusters. Conditional knockout of Atg5 in α-SMA+ CAFs promoted inflammatory re-programming in CAFs, reduced Treg cell infiltration and attenuated tumour development. Overall, our findings reveal an immunosuppressive mechanism entailing the formation of synapses between α-SMA+ CAFs and Tregs in an autophagy-dependent manner

Increased expression of phosphorrylated NBS1, a key molecule of the DNA damage response machinery, is an adverse prognostic factor in patients with de novo myelodysplastic syndromes

The expression of activated forms of key proteins of the DNA damage response machinery (pNBS1, pATM and γH2AX) was assessed by means of immunohistochemistry in bone marrow biopsies of 74 patients with de novo myelodysplastic syndromes (MDS) and compared with 15 cases of de novo acute myeloid leukemia (AML) and 20 with reactive bone marrow histology. Expression levels were significantly increased in both MDS and AML, compared to controls, being higher in high-risk than in low-risk MDS. Increased pNBS1 and γH2AX expression possessed a significant negative prognostic impact for overall survival in MDS patients, whereas pNBS1 was an independent marker of poor prognosis

Recent advances in intestinal lymphomas

A large variety of lymphoma types may develop as primary intestinal neoplasms in the small intestines or, less often, in the colorectum. Among these are a few entities such as enteropathy-associated T-cell lymphoma or immunoproliferative small intestinal disease that, essentially, do not arise elsewhere than in the gastrointestinal tract. In most instances the primary intestinal lymphomas belong to entities that also occur in lymph nodes or other mucosal sites, and may show some peculiar features. In the case of follicular lymphoma, important differences exist between the classical nodal cases and the intestinal cases, considered as a variant of the disease. It is likely that the local intestinal mucosal microenvironment is a determinant in influencing the pathobiological features of the disease. In this review we will present an update on the clinical, pathological and molecular features of the lymphoid neoplasms that most commonly involve the intestines, incorporating recent developments with respect to their pathobiology and classification. We will emphasize and discuss the major differential diagnostic problems encountered in practice, including the benign reactive or atypical lymphoid hyperplasias, indolent lymphoproliferative disorders of T or natural killer (NK) cells, and Epstein-Barr virus (EBV)-related lymphoproliferations

Interrogating the interplay of angiogenesis and immunity in metastatic colorectal cancer.

Colon cancer is the third most common malignancy and the fifth most frequent cause of death from neoplastic disease worldwide. At the time of diagnosis, more than 20% of patients already have metastatic disease. In the last 20 years, the natural course of the disease has changed due to major changes in the management of metastatic disease such as the advent of novel surgical and local therapy approaches as well as the introduction of novel chemotherapy drugs and targeted agents such as anti-epidermal growth factor receptor, anti-BRAF and antiangiogenics. Angiogenesis is a complex biological process of new vessel formation from existing ones and is an integral component of tumor progression supporting cancer cells to grow, proliferate and metastasize. Many molecules are involved in this proangiogenic process, such as vascular endothelial growth factor and its receptors on endothelial cells. A well-standardized methodology that is applied to assess angiogenesis in the tumor microenvironment is microvascular density by using immunohistochemistry with antibodies against endothelial CD31, CD34 and CD105 antigens. Even smaller molecules, such as the microRNAs, which are small non-coding RNAs, are being studied for their usefulness as surrogate biomarkers of angiogenesis and prognosis. In this review, we will discuss recent advances regarding the investigation of angiogenesis, the crosstalk between elements of the immune microenvironment and angiogenesis and how a disorganized tumor vessel network affects the trafficking of CD8+ T cells in the tumor bed. Furthermore, we will present recent data from clinical trials that combine antiangiogenic therapies with immune checkpoint inhibitors in colorectal cancer

Oral lichen planus as a preneoplastic inflammatory model. Journal of biomedicine & biotechnology 2012

Oral lichen planus (OLP) is a chronic oral inflammatory disease of unknown etiology. According to reports, 1-2% of OLP patients develop oral squamous cell carcinoma (OSCC) in the long run. While World Health Organization (WHO) classifies OLP as "a potentially malignant disorder," it is still a matter of debate which mechanisms drive OLP to such a condition. The current hypothesis connecting OLP and OSCC is that chronic inflammation results in crucial DNA damage which over time results in cancer development. Initial studies investigating the OLP and OSCC link were mainly retrospective clinical studies. Over the past years, several amount of information has accumulated, mainly from molecular studies on the OLP malignant potential. This article is a critical review of whether OLP has a malignant potential and, therefore, represents a model of preneoplastic inflammation

Transforming Growth Factor-beta 1/Smad Signaling in Glomerulonephritis and Its Association with Progression to Chronic Kidney Disease

Introduction: Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine, with diverse roles in fibrosis and inflammation, which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-beta/Smad signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD). Methods: We evaluated the immunohistochemical expression of TGF-beta 1, phosphorylated Smad3 (pSmad3), and Smad7 semiquantitatively and quantitatively using computerized image analysis program in different compartments of 50 renal biopsies with GN, and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression, and their role in progression to CKD. Results: TGF-beta 1 expression correlated positively with segmental glomerulosclerosis (p= 0.025) and creatinine level at diagnosis (p = 0.002), while pSmad3 expression with interstitial inflammation (p = 0.024). In glomerulus, concomitant expressions of high Smad7 and medium pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (p = 0.011), intense interstitial inflammation (p = 0.029), and lower serum complement (C) 3 (p = 0.028) and C4 (p = 0.029). We also reported a significant association between pSmad3 expression in glomerular endothelial cells of proliferative GN (p = 0.045) and in podocytes of nonproliferative GN (p = 0.005). Finally, on multivariate Cox-regression analysis, TGF-beta 1 expression (hazard ratio = 6.078; 95% confidence interval: 1.168-31.627; p = 0.032) was emerged as independent predictor for CKD. Discussion/Conclusion: TGF-beta 1/Smad signaling is upregulated with specific characteristics in different forms of GN. TGF-beta 1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation. (C) 2021 S. Karger AG, Base