Immunomodulation of T Helper Cells by Tumor Microenvironment in Oral Cancer Is Associated With CCR8 Expression and Rapid Membrane Vitamin D Signaling Pathway.

The immune system plays a key role in the protective response against oral cancer; however, the tumor microenvironment (TME) impairs this anti-cancer response by modulating T helper (Th) responses and promoting an anti-inflammatory environment. Regulatory T cells (Tregs) and Th2 effector cells (Teff) are associated with poor prognosis in oral squamous cell carcinoma (OSCC). However, the main immunomodulatory mechanisms associated with the enrichment of these subsets in OSCC remain unknown. We characterized Th-like lineages in Tregs and Teff and evaluated immunomodulatory changes induced by the TME in OSCC. Our phenotypic data revealed a higher distribution of tumour-infiltrating CCR8+ and Th2-like Treg in OSCC compared with non-malignant samples, whereas the percentages of Th1 cells were reduced in cancer. We then analyzed the direct effect of the TME by exposing T cell subsets to cancer secretomes and observed the OSCC secretome induced CCR8 expression and reduced cytokine production from both subsets. Transcriptomic analysis showed that the co-culture with OSCC secretome induced several gene changes associated with the vitamin D (VitD) signaling pathway in T cells. In addition, proteomic analysis identified the presence of several proteins associated with prostaglandin E2 (PGE2) production by rapid membrane VitD signaling and a reduced presence of the VitD binding protein. Thus, we analyzed the effect of VitD and PGE2 and observed that VitD promotes a regulatory Th2-like response with CCR8 expression whilst PGE2 also modulated CCR8 but inhibited cytokine production in combination with VitD. Finally, we evaluated the presence of CCR8 ligand in OSCC and observed increased chemokine CCL18, which was also able to upregulate CCR8 in activated Th cells. Overall, our data showed the immunomodulatory changes induced by the TME involving CCR8 expression and regulatory Th2 phenotypes, which are associated with PGE2 mediated VitD signaling pathway and CCL18 expression in OSCC.

Una experiencia de orientación desde el Telecentro de Pinar del Río / An orientation experience from the Pinar del Río Telecentre

RESUMEN • Introducción: La investigación responde a la necesidad de ampliar y diversificar la orientación psicológica que se ofrece a la población pinareña a través del medio televisivo, con énfasis en las familias que se encuentran inmersas en situaciones de emigración. Objetivo: diseñar el programa televisivo Conversemos, como propuesta de orientación psicológica dirigida a familias en situaciones de emigración, para contribuir a su funcionamiento adecuado. Métodos: se realizó un estudio transversal que combinó elementos descriptivos y explicativos, con la aplicación de los métodos histórico-lógico, modelación, sistémico estructural, entrevista, encuesta y análisis documental. Se desarrolló un diagnóstico en la televisión de Pinar del Río Resultados: se corroboró que la motivación de los implicados hacia el tema de la familia en situaciones de emigración fue adecuada, no así la satisfacción con su tratamiento actual, la cual se manifestó baja. El conocimiento en los especialistas fue elevado, limitado en los directivos y la teleaudiencia. Se diseñó el programa televisivo Conversemos, para ofrecer a la teleaudiencia pinareña un espacio de orientación que desarrollara habilidades y recursos para afrontar exitosamente la problemática migratoria. Conclusión: la orientación psicológica que se ofrecía en la televisión pinareña hacia la familia en situaciones de emigración, resultó insuficiente. Se evidenció elevada motivación hacia el tema por parte de la teleaudiencia y los especialistas, quienes poseen conocimiento adecuado sobre el tema, limitado por parte de la teleaudiencia y los directivos del telecentro, lo que determinó niveles bajos de satisfacción en todos los implicados.

ABSTRACT • Introduction: the research responds to the need to broaden and diversify the psychological counseling offered to the population of Pinar del Río through television, with emphasis on families that are in situations of immigration. Objective: to design the television program Conversemos (Let's Talk), as a proposal of psychological counseling directed to families in situations of immigration, in order to contribute to family satisfactory functioning. Methods: a cross-sectional study was carried out that combined descriptive and explanatory elements, with the application of historical-logical methods, modeling, structural-systemic, interview, survey and documentary analysis. A diagnosis was developed in the telecenter of Pinar del Río province, Cuba. Results: it was corroborated that the motivation of those involved on the subject of family in situations of immigration was satisfactory, but not the satisfaction with its current treatment, which was low. Knowledge level of the specialists was high, but the level of knowledge of the directors and the audience was limited. The TV-program Let's Talk was designed to offer to Pinar del Río audience a space for counseling that would develop skills and resources to cope successfully with the immigration problem. Conclusion: the psychological counseling offered by Pinar del Río telecenter to the family in situations of immigration was insufficient. There was a high level of motivation towards the subject on the part of the audience and the specialists, who had adequate knowledge on the subject, but limited level of knowledge on the part of the audience and the directors of the telecenter, which determined low levels of satisfaction in all people involved.