RESUMEN

INTRODUCTION: EBV infection in nasopharyngeal cancer ensued in latent infection mode. In this latent infection various EBV oncoproteins such as EBNA1 and LMP1 was expressed. EBV oncoproteins could theoretically recruit immune cells, which might help to control cancer. Therefore, this study was aimed to elucidate the association with EBV oncoproteins (EBNA1 and LMP1), immune markers (CD4, CD8, and FOXP3) from nasopharyngeal cancer microenvironment with tumor progression. METHOD: Nasopharyngeal biopsy was obtained from patients suspected to have nasopharyngeal cancer. Those samples with microscopically confirmed nasopharyngeal cancer were tested for EBNA1, LMP1, CD4, CD8, and FOXP3 concentration with ELISA, then verified with IHC. Each patient tumor volume was assessed for primary nasopharyngeal tumor volume (GTVp) and neck nodal metastases tumor volume (GTVn). Correlation test with Spearman correlation and scatterplot were carried out. RESULT: Total 23 samples with nasopharyngeal cancer were analyzed. There was moderate correlation (ρ = 0.45; p value = 0.032) between LMP1 and GTVp. There was strong correlation (ρ = 0.81; p value < 0.001) between CD8 and GTVp. There was also moderate correlation (ρ = 0.6; p value = 0.002) between FOXP3 and GTVp. The CD8 concentration has moderate correlation with both EBNA1 (ρ = 0.46; p value = 0.026) and LMP1 (ρ = 0.47; p value = 0.023). While FOXP3 has moderate correlation with only LMP1 (ρ = 0.58; p value = 0.004). No correlation was found between all the markers tested here with GTVn. DISCUSSION: We found larger primary nasopharyngeal tumor was associated with higher CD8 marker. This was thought due to the presence of abundance CD8 T cells in the nasopharynx, but those abundance CD8 T cells were suspected to be dysfunctional. The nasopharyngeal cancer was also known to upregulate chemokines that could recruit T regulatory FOXP3 cells. Furthermore, T regulatory FOXP3 cells differentiation was induced through several pathways which was triggered by EBNA1. The correlation found in this study could guide further study to understand nasopharyngeal carcinogenesis and the relationship with our immune system.

Asunto(s)

Carcinoma , Infecciones por Virus de Epstein-Barr , Infección Latente , Neoplasias Nasofaríngeas , Biomarcadores , Carcinogénesis , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/metabolismo , Factores de Transcripción Forkhead , Herpesvirus Humano 4 , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patología , Proteínas Oncogénicas , Microambiente Tumoral , Proteínas de la Matriz Viral

RESUMEN

Tumor microenvironment have been implicated in many kind of cancers to hold an important role in determining treatment success especially with immunotherapy. In nasopharyngeal cancer, the prognostic role of this immune cells within tumor microenvironment is still doubtful. We conducted a study that included 25 nasopharyngeal cancer biopsy specimens to seek a more direct relationship between tumor infiltrating immune cells and tumor progression. Apart from that, we also checked the PD-L1 protein through immunohistochemistry. The PD-L1 was positively expressed in all our 25 samples with nasopharyngeal cancer WHO type 3 histology. Majority samples have >50% PD-L1 expression in tumor cells. We also found that denser local tumor infiltrating immune cells population have relatively much smaller local tumor volume. The inverse applied, with the mean local tumor volumes were 181.92 cm3 ± 81.45 cm3, 117.13 cm3 ± 88.72 cm3, and 55.13 cm3 ± 25.06 cm3 for mild, moderate, and heavy immune cells infiltration respectively (p = 0.013). Therefore, we concluded that tumor infiltrating immune cells play an important role in tumor progression, hence evaluating this simple and predictive factor may provide us with some valuable prognostic information.

Asunto(s)

Antígeno B7-H1/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Microambiente Tumoral , Femenino , Humanos , Linfocitos Infiltrantes de Tumor/patología , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/inmunología , Carga Tumoral

RESUMEN

Nasopharyngeal cancer is a cancer closely related to Epstein-Barr virus (EBV) infection. EBV protein has been shown to be related to various oncogenic development. Suppression of tumor suppressor genes, upregulating molecules to prevent immune attack, downregulating pro-apoptotic proteins, and stimulating local immune suppressive environment are among some roles that EBV proteins can exert on host cells. All those factors combined together with underlying genetic susceptibility of host cells further increase the chance of nasopharyngeal cancer development. Approach targeting those carcinogenesis pathways has been tested with marginal benefit. A newer approach boosting immune cells to increase recognition of tumor antigen and promoting cytotoxic T cell attack has shown promising clinical benefit. Further combination of those immunotherapies with other modality, in particular radiotherapy, has resulted in amplification of cancer killing.