The Role of Regulatory T Cells in Cancer Treatment Resistance.

Despite tremendous progress in cancer treatment in recent years, treatment resistance is still a major challenge for a great number of patients. One of the main causes is regulatory T lymphocytes (Tregs), which suppress excessive inflammatory responses via the secretion of immunosuppressive cytokines and upregulate the immune checkpoints. Their abundance causes an immunosuppressive reprogramming of the tumor environment, which is ideal for tumor growth and drug inefficiency. Hence, regiments that can regain tumor immunogenicity are a promising strategy to overcome Tregs-mediated drug resistance. However, to develop effective therapeutic regimens, it is essential to understand the molecular mechanisms of Treg-mediated resistance. In this article, we gathered a comprehensive summary of the current knowledge on molecular mechanisms and the role of Tregs in cancer treatment resistance, including cancer immunotherapy, targeted therapy, chemotherapy, and radiotherapy.

VISTA H-Score Is Significantly Associated with a 5-Year DFS Rate in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer in the world. Despite its prevalence, it is often recognized in advanced stages (III or IV) when it has already spread to local lymph nodes. In this study, we investigate the V-domain Ig suppressor of T cell activation (VISTA) as a potential prognostic factor in OSCC. Tissue samples were collected from 71 oral squamous cell carcinoma patients to determine protein expression levels (using immunochemistry and the semi-quantitative H-score method). Moreover, RT-qPCR was additionally performed in 35 patients. Clinical factors in our cohort study had no impact on VISTA expression. However, VISTA expression is largely correlated with Il-33 levels in tumor cells and lymphocytes and with PD-L1 in tumor cells. The impact of VISTA expression on overall survival (OS) is rather limited, but in the case of a 5-year survival rate, a significant association has been proven. VISTA seems to be a rather weak clinicopathological marker but needs further evaluation in the context of survival. In addition, the potential of VISTA combination with Il-33 or PD-L1 should be further investigated in OSCC.

Management of Pheochromocytomas and Paragangliomas: A Case-Based Review of Clinical Aspects and Perspectives.

Paraganglioma and pheochromocytoma are rare medical conditions. Thus, there are still a small number of studies, clinical trials, and evidence-based data in this field. This makes clinical decisions more difficult. In this study, we present a case report enriched with a short review of available essential clinical data, indicating the need for constant metoxycatecholamine level observation and a proper diagnostic imaging approach, especially in terms of ongoing pandemics. Our research also provides a summary of the molecular background of these diseases, indicating their future role in clinical management. We analyzed the ClinicalTrials.gov dataset in order to show future perspectives. In this paper, the use of the PET-CT before MRI or CT is proposed in specific cases during diagnosis processes contrary to the guidelines. PET-CT may be as effective as standard procedures and may provide a faster diagnosis, which is important in periods with more difficult access to health care, such as during the COVID-19 pandemic.

Molecular Mechanisms Leading from Periodontal Disease to Cancer.

Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigating tumorigenesis. We also present evidence for potential links between the RANKL-RANK signaling axis as well as circulating cytokines/leukocytes and carcinogenesis. Due to the nonconclusive data associating periodontitis and cancer reported in the case and cohort studies, we examine clinical trials relevant to the topic and summarize their outcome.

ZNF-281 as the Potential Diagnostic Marker of Oral Squamous Cell Carcinoma.

ZNF-281 is a zinc finger factor which can lead to cancer progression and metastasis. Its up-regulation reported in many cancers was correlated with metastasis and worsened patients' prognosis. This is the first study describing ZNF-281 in the context of OSCC. Oral tissue samples drawn from 66 OSCC patients and 36 control patients were collected to determine protein (using immunochemistry and the semi-quantitative H-score method) and mRNA expression levels (using the RT-qPCR reaction). Our aim was to assess the ZNF-281 expression level in OSCC and the control group. Moreover, we determined the impact of ZNF-281 on survival parameters and the association of diversified clinical parameters with ZNF-281 expression. Clinical factors such as grade, AJCC stage and radiotherapy have an impact on the ZNF-281 H-score level, whereas AJCC stage and grade have an influence on ZNF-281 mRNA expression. Our survival analysis indicated that the impact on overall survival is not statistically significant, and the prognostic potential of ZNF-281 is rather limited. Our findings show that both levels of the ZNF-281 H-score and mRNA are decreased in OSCC in comparison to normal tissue. Moreover, we estimated that the H-score can differentiate normal tissue from OSCC with a sensitivity of 97% and specificity of 93.7%.