RESUMO
Plasma gelsolin (pGSN) overexpression in ovarian cancer (OVCA) disarms immune function, contributing to chemoresistance. The aim of this study was to investigate the immunoregulatory effects of pGSN expression on natural killer (NK) cell function in OVCA. OVCA tissues from primary surgeries underwent immunofluorescent staining of pGSN and the activated NK cell marker natural cytotoxicity triggering receptor 1 to analyze the prognostic impact of pGSN expression and activated NK cell infiltration. The immunoregulatory effects of pGSN on NK cells were assessed using apoptosis assay, cytokine secretion, immune checkpoint-receptor expression, and phosphorylation of STAT3. In OVCA tissue analyses, activated NK cell infiltration provided survival advantages to patients. However, high pGSN expression attenuated the survival benefits of activated NK cell infiltration. In the in vitro experiment, pGSN in OVCA cells induced NK cell death through cell-to-cell contact. pGSN increased T-cell immunoglobulin and mucin-domain-containing-3 expression (TIM-3) on activated NK cells. Further, it decreased interferon-γ production in activated TIM-3+ NK cells, attenuating their anti-tumor effects. Thus, increased pGSN expression suppresses the anti-tumor functions of NK cells. The study provides insights into why immunotherapy is rarely effective in patients with OVCA and suggests novel treatment strategies.
Assuntos
Carcinoma Epitelial do Ovário , Resistencia a Medicamentos Antineoplásicos , Gelsolina , Células Matadoras Naturais , Neoplasias Ovarianas , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Feminino , Gelsolina/metabolismo , Gelsolina/sangue , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/imunologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Linhagem Celular Tumoral , Pessoa de Meia-Idade , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Apoptose/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Interferon gama/metabolismoRESUMO
BACKGROUND: The aim of this study was to evaluate the differences in the knowledge and attitude regarding silver diamine fluoride (SDF) between two groups, differentiated by whether they had experience in SDF use, of dental students and clinical trainee dentists in Japan. METHODS: A survey was designed consisting of three dental classes (fourth, fifth, and sixth years) and clinical trainees at Kyushu Dental University. A survey was designed consisting of 32 questions about the knowledge, attitudes, esthetic acceptability, and potential barriers regarding the use of SDF. RESULTS: A total of 286 surveys (response rate of 85.4%) were collected. Among all respondents, 21.7% had experience with SDF use in their clinical practice. Regarding the knowledge score for SDF (0 to 12 points), in the respondents with no experience of using SDF, the mean score was 3.06, and that of respondents with experience of using SDF was 1.66, which was a significant difference (p < 0.001). The mean esthetic acceptability score for SDF use (-8 to 8 points) of the clinical trainees was -1.00 and that of the fourth-year students was 0.74, which was a significant difference (p < 0.05). CONCLUSIONS: the results indicate that dental students and clinical trainees need to increase their clinical experience with SDF.